Showing papers in "Parasite Immunology in 2014"

Immunology of human schistosomiasis.

Abstract: There is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas: immunopathogenesis, resistance to reinfection and diagnostics. It is clear that the bulk of, if not all, morbidity due to human schistosomiasis results from immune-response-based inflammation against eggs lodged in the body, either as regulated chronic inflammation or resulting in fibrotic lesions. However, the exact nature of these responses, the antigens to which they are mounted and the mechanisms of the critical regulatory responses are still being sorted out. It is also becoming apparent that protective immunity against schistosomula as they develop into adult worms develops slowly and is hastened by the dying of adult worms, either naturally or when they are killed by praziquantel. However, as with anti-egg responses, the responsible immune mechanisms and inducing antigens are not clearly established, nor are any potential regulatory responses known. Finally, a wide variety of immune markers, both cellular and humoral, can be used to demonstrate exposure to schistosomes, and immunologic measurement of schistosome antigens can be used to detect, and thus diagnose, active infections. All three areas contribute to the public health response to human schistosome infections.

Immunology of lymphatic filariasis

Abstract: The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen-specific Th2 response and an expansion of IL-10 producing CD4(+) T cells that is accompanied by a muted Th1 response. This antigen-specific T-cell hyporesponsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4(+) T-cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T-cell hyporesponsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general.

Immunoregulatory networks in human Chagas disease

Abstract: Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and thus influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies has led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks.

Pregnancy and helminth infections.

Abstract: It has been proposed that helminth infection may be particularly detrimental during pregnancy, through adverse effects on maternal anaemia and on birth outcomes, and that anthelminthic treatment during pregnancy will therefore be particularly beneficial. However, the few treatment trials that have been conducted have given, but little support to this notion and further trials in settings of nutritional stress are needed. It has also been proposed that prenatal exposure to helminth infection has an important effect on the development of the foetal immune response. There is evidence that this may impact, long-term, upon responses to helminth and nonhelminth antigens, and to allergens. Exposure to helminths in utero may also have nonspecific effects that may modify the offspring's susceptibility to diseases mediated by inflammation, including metabolic disorders. The mechanisms of such effects are not known, but they deserve to be explored as current epidemiological findings suggest the possibility of primary prevention for inflammatory conditions such as allergy, through intervention during pregnancy.

Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice.

Abstract: Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.

Protection and pathology during parasite infection: IL-10 strikes the balance.

Abstract: The host response to infection requires an immune response to be strong enough to control the pathogen but also restrained, to minimize immune-mediated pathology The conflicting pressures of immune activation and immune suppression are particularly apparent in parasite infections, where co-evolution of host and pathogen has selected many different compromises between protection and pathology Cytokine signals are critical determinants of both protective immunity and immunopathology, and, in this review, we focus on the regulatory cytokine IL-10 and its role in protozoan and helminth infections We discuss the sources and targets of IL-10 during parasite infection, the signals that initiate and reinforce its action, and its impact on the invading parasite, on the host tissue, and on coincident immune responses

Immunoregulation in human American leishmaniasis: balancing pathology and protection

Abstract: Leishmaniasis covers a broad spectrum of diseases with distinct, and sometimes overlapping, characteristics. The common thread in all forms of leishmaniasis is the infection by the parasite Leishmania belonging to the genus Leishmania. Upon infection of humans, there can be at least three outcomes, (i) control of Leishmania by the host immune response resulting in asymptomatic disease, (ii) patent infection and development of a relatively mild form of leishmaniasis and (iii) patent infection and development of severe clinical forms. The factors that determine the outcome of an initial inoculation with Leishmania are many, with the species of Leishmania representing one of the strongest predictive factors for the development of a given clinical form of disease. This is seen with L. braziliensis and L. amazonensis, infection leading mostly to tegumentary forms of disease, and L. infantum with the potential to induce visceral disease. However, it is also clear that the host immune response is a key factor in disease progression, not only responsible for control of Leishmania, but also playing an important role in disease progression and pathology. This duality between protective and pathogenic immune responses in individuals infected with Leishmania in the Americas is the focus of this review.

Host resistance in cattle to infestation with the cattle tick Rhipicephalus microplus

Abstract: Resistance to Rhipicephalus microplus infestation in cattle has many effector mechanisms, each of which is likely to be modulated by complex, interacting factors. Some of the mechanisms of host resistance and their modulating factors have been identified and quantified, although much remains to be explained. The variation in resistance to tick infestation is most marked between Bos taurus and Bos indicus cattle, taurine cattle given the same exposure carrying between five and 10 times as many ticks as indicine cattle. Tick resistance is mostly manifest against attaching larvae, which attempt to feed often and without success, death occurring mostly within 24 h of finding a host. There is evidence of innate and adaptive immune response to tick infestation, and it appears that the relative importance of each differs between indicine and taurine cattle. There is conflicting information regarding the role of humoral immunity in tick resistance, and recent studies indicate that strong IgG responses to tick antigens are not protective. A strong T-cell-mediated response directed against larval stages, as mounted by indicine cattle, seems to be protective. Variation in the extracellular matrix of skin (epidermal growth factors, collagens and other matrix components such as lumican) also contributes to variation in host resistance.

Mucosal immune responses following intestinal nematode infection

Abstract: SUMMARY In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1–2 years) (1). Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 25 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) (1, 2). Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host–helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed.

Immunology of Taenia solium taeniasis and human cysticercosis

Abstract: The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by faecal-oral contamination Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time Moreover, existing data are limited by the relative lack of animal models This manuscript revises the available information on the immunology of human taeniasis and cysticercosis

Parasitic scabies mites and associated bacteria joining forces against host complement defence.

Abstract: Scabies is a ubiquitous and contagious skin disease caused by the parasitic mite Sarcoptes scabiei Epidemiological studies have identified scabies as a causative agent for secondary skin infections caused by Staphylococcus aureus and Streptococcus pyogenes. This is an important notion, as such bacterial infections can lead to serious downstream life-threatening complications. As the complement system is the first line of host defence that confronts invading pathogens, both the mite and bacteria produce a large array of molecules that inhibit the complement cascades. It is hypothesised that scabies mite complement inhibitors may play an important role in providing a favourable micro-environment for the establishment of secondary bacterial infections. This review aims to bring together the current literature on complement inhibition by scabies mites and bacteria associated with scabies and to discuss the proposed molecular link between scabies and bacterial co-infections.

A multivalent chimeric vaccine composed of Schistosoma mansoni SmTSP-2 and Sm29 was able to induce protection against infection in mice.

Abstract: Schistosoma mansoni is a blood fluke parasite responsible for schistosomiasis. The best long-term strategy to control schistosomiasis is through immunization combined with drug treatment. In this study, we cloned, expressed and purified SmTSP-2 fused to the N- and C-terminal halves of Sm29 and tested these chimeras as vaccine candidates using an adjuvant approved to be used in humans. The results demonstrated that vaccination with SmTSP-2 fused to N- or C-terminus of Sm29-induced reduction in worm burden and liver pathology when compared to control animals. Additionally, we detected high levels of mouse-specific IgG, IgG1 and IgG2a against both chimeras and significant amounts of IFN-γ and TNF-α and no IL-4. Finally, studies with sera from patients resistant to infection and living in schistosomiasis endemic areas revealed high levels of specific IgG to both chimeras when compared to healthy individuals. In conclusion, SmTSP-2/Sm29 chimeras tested here induced partial protection against infection and might be a potential vaccine candidate.

Helminths in the lungs

Abstract: Parasitic helminths infect well over one billion people and typically cause chronic and recurrent infections that exert a considerable toll on human health and productivity. A significant number of important intestinal- and tissue-dwelling helminth parasites have evolved a scripted migration through select organ systems. Of specific interest here are the helminth parasites that interact with respiratory tissues and the pulmonary immune system. This review will consider the nature of the interactions between helminth parasites and the lung environment, as well as the consequences of these interactions on the evolution of parasitism and host immunity.

Chronic Trypanosoma congolense infections in mice cause a sustained disruption of the B‐cell homeostasis in the bone marrow and spleen

Abstract: Trypanosoma congolense is one of the main species responsible for Animal African Trypanosomosis (AAT). As preventive vaccination strategies for AAT have been unsuccessful so far, investigating the mechanisms underlying vaccine failure has to be prioritized. In T. brucei and T. vivax infections, recent studies revealed a rapid onset of destruction of the host B-cell compartment, resulting in the loss of memory recall capacity. To assess such effect in experimental T. congolense trypanosomosis, we performed infections with both the cloned Tc13 parasite, which is considered as a standard model system for T. congolense rodent infections and the noncloned TRT55 field isolate. These infections differ in their virulence level in the C57BL/6 mouse model for trypanosomosis. We show that early on, an irreversible depletion of all developmental B cells stages occur. Subsequently, in the spleen, a detrimental decrease in immature B cells is followed by a significant and permanent depletion of Marginal zone B cells and Follicular B cells. The severity of these events later on in infection correlated with the virulence level of the parasite stock. In line with this, it was observed that later-stage infection-induced IgGs were largely nonspecific, in particular in the more virulent TRT55 infection model.

Crusted scabies is associated with increased IL-17 secretion by skin T cells.

Abstract: Scabies is an ectoparasitic infestation by the mite Sarcoptes scabiei. Although commonly self-limiting, a fraction of patients develop severely debilitating crusted scabies. The immune mechanisms underlying the development of crusted scabies are unclear, and undertaking longitudinal infection studies in humans is difficult. We utilized a porcine model to compare cellular immune responses in peripheral blood and skin of pigs with different clinical manifestations of scabies (n = 12), and in uninfected controls (n = 6). Although clinical symptoms were not evident until at least 4 weeks post-infestation, the numbers of peripheral IFNγ-secreting CD4+ T cells and γδ T cells increased in infected pigs from week 1 post-infestation. γδ T cells remained increased in the blood at week 15 post-infestation. At week 15, skin cell infiltrates from pigs with crusted scabies had significantly higher CD8+ T cell, γδ T cell and IL-17+ cell numbers than those with ordinary scabies. Peripheral IL-17 levels were not increased, suggesting that localized skin IL-17-secreting T cells may play a critical role in the pathogenesis of crusted scabies development. Given the potential of anti-IL-17 immunotherapy demonstrated for other inflammatory skin diseases, this study may provide a novel therapeutic avenue for patients with recurrent crusted scabies.

Fasciola hepatica tegumental antigens indirectly induce an M2 macrophage‐like phenotype in vivo

Abstract: Summary The M2 subset of macrophages has a critical role to play in host tissue repair, tissue fibrosis and modulation of adaptive immunity during helminth infection. Infection with the helminth, Fasciola hepatica, is associated with M2 macrophages in its mammalian host, and this response is mimicked by its excretory-secretory products (FhES). The tegumental coat of F. hepatica (FhTeg) is another major source of immune-modulatory molecules; we have previously shown that FhTeg can modulate the activity of both dendritic cells and mast cells inhibiting their ability to prime a Th1 immune response. Here, we report that FhTeg does not induce Th2 immune responses but can induce M2-like phenotype in vivo that modulates cytokine production from CD4+ cells in response to anti-CD3 stimulation. FhTeg induces a RELMα expressing macrophage population in vitro, while in vivo, the expression of Arg1 and Ym-1/2 but not RELMα in FhTeg-stimulated macrophages was STAT6 dependent. To support this finding, FhTeg induces RELMα expression in vivo prior to the induction of IL-13. FhTeg can induce IL-13-producing peritoneal macrophages following intraperitoneal injection This study highlights the important role of FhTeg as an immune-modulatory source during F. hepatica infection and sheds further light on helminth–macrophage interactions.

Giardia lamblia binding immunoglobulin protein triggers maturation of dendritic cells via activation of TLR4-MyD88-p38 and ERK1/2 MAPKs.

Abstract: Much remains unknown about the mammalian immune response to Giardia lamblia, a protozoan pathogen that causes diarrhoeal outbreaks. We fractionated protein extracts of G. lamblia trophozoites by Viva-spin centrifugation, DEAE ion exchange and gel filtration chromatography. Resultant fractions were screened for antigenic molecules by western blots analysis using anti-G. lamblia antibodies (Abs), resulting in identification of G. lamblia binding immunoglobulin protein (GlBiP). Maturation of mouse dendritic cells (DCs) in response to recombinant GlBiP (rGlBiP) was detected by increased expression of surface molecules such as CD80, CD86 and MHC class II; these mature DCs, produced pro-inflammatory cytokines (TNF-α, IL-12 and IL-6). Especially, the truncated rGlBiP containing the heat-shock protein 70 domain-induced cytokine production from mouse DCs. rGlBiP-induced DC activation was initiated by TLR4 in a MyD88-dependent way and occurred through activation of p38 and ERK1/2 MAPKs as well as increased activity of NF-κB and AP-1. Moreover, CD4(+) T cells stimulated with rGlBiP-treated DCs produced high levels of IL-2 and IFN-γ. Together, our results suggest that GlBiP contributes to maturation of DCs via activation of TLR4-MyD88-p38, ERK1/2 MAPK, NF-κB and AP-1.

Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella spiralis and Trichinella pseudospiralis infections in mice.

Abstract: Summary Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the host-parasite relationship such as the inflammatory response in parasitized muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent a marker of inflammation since they regulate inflammation and immunity. The aim of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2) in mice experimentally infected with T. spiralis or T. pseudospiralis, to elucidate the involvement of these molecules during the inflammatory response to these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess the serum levels and in situ zymography on muscle histological sections to show the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9 serum level increased 6 days post-infection whereas, the total MMP-2 serum level increased onward. A similar trend was observed in T. pseudospiralis infected mice but the MMP-9 level was lower than that detected in T. spiralis infected mice. Significant differences were also observed in MMP-2 levels between the two experimental groups. The number of gelatinase positive cells was higher in T. spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and MMP-2 are markers of the inflammatory response for both T. spiralis and T. pseudospiralis infections.

Apicomplexan infections in the gut

Abstract: Summary Toxoplasma gondii and Cryptosporidium parvum are intracellular protozoan parasites that establish infection through the small intestinal bowel after the ingestion of contaminated food products. These Apicomplexan parasites have emerged as an important cause of chronic and fatal disease in immunodeficient individuals, in addition to being investigated as possible triggers of inflammatory bowel disease. T. gondii disseminates to the brain and other tissues after infection, whereas C. parvum remains localized to the intestine. In the following review, we will discuss the pathogenesis of these parasitic diseases in the small intestine, the site of initial invasion. Themes include the sequence of invasion, the structure of Th1 immunity provoked by these parasites and the contribution of intestinal microbiota to the development of the mucosal immune response.

Immune responses to Schistosoma haematobium infection

Abstract: Urogenital schistosomiasis is one of the greatest single infectious sources of human morbidity and mortality known. Through a complex cycle of infection, migration and eventual maturation and mating, S. haematobium (the aetiological agent of urogenital schistosomiasis) deposits highly immunogenic eggs within the bladder and other pelvic organs, activating a wide range of immune programs that determine both infection outcome as well as downstream immunopathology. In this review, we discuss the experimental and observational bases for our current understanding of these immune programs, focusing specifically on how the balance of type 1 and type 2 responses governs subsequent immunopathology and clinical outcome.

RNA interference for the identification of ectoparasite vaccine candidates.

Abstract: Ectoparasites present a major challenge for disease management globally. With drug resistance increasingly observed in many disease-causing species, the need for novel control measures is pressing. Ever-expanding genomic resources from 'next generation' sequencing are now available for a number of arthropod ectoparasites, necessitating an effective means of screening these data for novel candidates for vaccine antigens or targets for chemotherapeutics. Such in vitro screening methods must be developed if we are to make discoveries in a timely and cost-effective manner. This review will discuss the potential that RNA interference (RNAi) has demonstrated thus far in the context of arthropod ectoparasites and the potential roles for this technology in the development of novel methods for parasite control.

Immunodiagnosis of sheep infections with Echinococcus granulosus: in 35 years where have we come?

Abstract: W. K. Yong and D. D. Heath published in 1979 a seminal paper in the first issue of Parasite immunology describing their efforts to determine whether the arc 5 precipitin band, formed when test human serum is reacted against electrophoresed hydatid cyst fluid antigen, would be a suitable immunodiagnostic test for the identification of sheep infected with Echinococcus granulosus. Although they found antibodies to arc 5 in the sera of hydatid-infected sheep, the sera of some sheep harbouring Taenia ovis and T. hydatigena also precipitated the hydatid cyst fluid arc 5 antigen, so they concluded arc 5 antibodies were not suitable for the specific immunodiagnosis of E. granulosus infection in sheep in New Zealand. Subsequent work has shown that the existence of multiple infections with different taeniid species, antigenic cross-reactivity between these related parasites and the low level of specific antibody response to infection continue to hinder efforts to improve the diagnosis of hydatid infection in sheep and other natural intermediate hosts, thereby preventing the development of any practical test. In particular, the poor antibody response of ruminants to naturally acquired hydatid infection may prove an insurmountable barrier in future efforts to develop a reliable and accurate immunological test.

Understanding the role of antibodies in murine infections with Heligmosomoides (polygyrus) bakeri: 35 years ago, now and 35 years ahead

Abstract: The rodent intestinal nematode H.p.bakeri has played an important role in the exploration of the host–parasite relationship of chronic nematode infections for over six decades, since the parasite was first isolated in the 1950s by Ehrenford. It soon became a popular laboratory model providing a tractable experimental system that is easy to maintain in the laboratory and far more cost-effective than other laboratory nematode–rodent model systems. Immunity to this parasite is complex, dependent on antibodies, but confounded by the parasite's potent immunosuppressive secretions that facilitate chronic survival in murine hosts. In this review, we remind readers of the state of knowledge in the 1970s, when the first volume of Parasite Immunology was published, focusing on the role of antibodies in protective immunity. We show how our understanding of the host–parasite relationship then developed over the following 35 years to date, we propose testable hypotheses for future researchers to tackle, and we speculate on how the new technologies will be applied to enable an increasingly refined understanding of the role of antibodies in host-protective immunity, and its evasion, to be achieved in the longer term.

Leishmania braziliensis amastigotes stimulate production of IL‐1β, IL‐6, IL‐10 and TGF‐β by peripheral blood mononuclear cells from nonendemic area healthy residents

Abstract: Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1β, IL-6, TGF-β and IL-23 production, whereas IL-10 and TGF-β are associated with tissue protection Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17 Seven L (V) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1β, IL-6 and TGF-β These data demonstrate for the first time that L (V) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17

B‐cell epitopes of antigenic proteins in Leishmania infantum: an in silico analysis

Abstract: Summary Serodiagnosis of visceral leishmaniasis is often hindered by cross-reactions to other parasitic diseases. Identifying specific B-cell epitopes in proteins is therefore important for immunodiagnostics, as well as for disease control by vaccines. This study aimed to identify linear and conformational B-cell epitopes and to evaluate the secondary structure of antigen proteins in Leishmania infantum using in silico analysis. Linear epitopes were predicted using the Immune Epitope Database and Analysis Resource (IEDB), BepiPred and BcePred programs. The conformational B-cell epitopes were identified using the CBTOPE server. The combination of the predictions using IEDB, BepiPred and BcePred generated 148 linear epitopes from the calpain-like cysteine peptidase (CP), thiol-dependent reductase 1 (TDR1) and HSP70 proteins. In total, 164 conformational epitopes were predicted, mostly located in the linear epitope region. The predicted epitopes are located in α helix and random coil regions in the thiol-dependent reductase 1 and HSP70 proteins. New linear and conformational B-cell epitopes of L. infantum proteins were identified in silico, and the prediction using various programs ensures greater accuracy of the results, as suggested by confirmation of previously identified HSP70 epitopes.

Immune response in susceptible BALB/c mice immunized with DNA encoding Lipophosphoglycan 3 of Leishmania infantum

Abstract: Visceral leishmaniasis is a serious parasitic infection that the development of an effective vaccine is necessary to control the disease. Lipophosphoglycan 3 (LPG3) is essential for the synthesis of glycoconjugates as parasite virulence factors. In this study, we evaluated the immunogenicity of Leishmania infantum LPG3 gene as a DNA vaccine against murine visceral leishmaniasis. For this purpose, BALB/c mice were immunized subcutaneously with the DNA encoding LPG3 either alone or in combination with recombinant heat shock protein 70 (rHSP70). Next, its immunogenicity and protective efficacy were evaluated in the immunized mice. The results showed a mixed Th1/Th2 response following immunization, which was associated with the production of both IFN-γ and IL-10 by splenocytes compared with control groups but did not lead to reduction in the splenic parasite burden. Serum levels of IgG antibody isotypes indicated no significant difference between the LPG3 DNA and the empty vector. In addition, the co-administration of rHSP70 with the DNA vaccine offered no additive protective advantage on experimental infectious challenge. Thus, we propose to strengthen the immunogenic potential of L. infantum LPG3 in prime-boost approach with a powerful adjuvant to elicit a robust parasite-specific protective Th1 response.

Immunology of experimental and natural human hookworm infection.

Abstract: Human hookworm infection is one amongst the most prevalent of the neglected tropical diseases. An informative experimental animal model, that is, one that parallels a human infection, is not available for the study of human hookworm infection. Much of our current understanding of the human immune response during hookworm infection relies on the studies from experimental infection of hookworm-naive individuals or the natural infections from individuals residing in hookworm-endemic areas. The experimental human infections tend to be acute, dose-controlled infections, often with a low larval inoculum so that they are well tolerated by human volunteers. Natural hookworm infections usually occur in areas where hookworm transmission is constant and infection is chronic. In cases where there has been drug administration in an endemic area, re-infection often occurs quickly even amongst those who were treated. Hence, although many of the characteristics of experimental and natural hookworm infection differ, both models have elements in common: mainly an intense Th2 response with the production of total and specific IgE as well as elevated levels of eosinophilia, IL-5, IL-10 and TNF. While hookworm infection affects millions of individuals worldwide, much of the human immunology of this infection still needs to be studied and understood.

Protective immunity against malaria after vaccination.

Abstract: Summary A good understanding of the immunological correlates of protective immunity is an important requirement for the development of effective vaccines against malaria. However, this concern has received little attention even in the face of two decades of intensive vaccine research. Here, we review the immune response to blood-stage malaria, with a particular focus on the type of vaccine most likely to induce the kind of response required to give strong protection against infection.

Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity.

Abstract: Horses are affected by a wide variety of arthropod ectoparasites, ranging from lice which spend their entire life on the host, through ticks which feed over a period of days, to numerous biting insects that only transiently visit the host to feed. The presence of ectoparasites elicits a number of host responses including innate inflammatory responses, adaptive immune reactions and altered behaviour; all of which can reduce the severity of the parasite burden. All of these different responses are linked through immune mechanisms mediated by mast cells and IgE antibodies which have an important role in host resistance to ectoparasites, yet immune responses also cause severe pathological reactions. One of the best described examples of such pathological sequelae is insect bite hypersensitivity (IBH) of horses; an IgE-mediated type 1 hypersensitivity to the salivary proteins of Culicoides spp. associated with T-helper-2 production of IL4 and IL13. Importantly, all horses exposed to Culicoides have an expanded population of Culicoides antigen-specific T cells with this pattern of cytokine production, but in those which remain healthy, the inflammatory reaction is tempered by the presence of FoxP3+ CD4+ regulatory T cells that express IL10 and TGF-beta, which suppresses the IL4 production by Culicoides antigen-activated T cells.

Antibodies are involved in the protective immunity induced in mice by Schistosoma mansoni schistosomula tegument (Smteg) immunization.

Abstract: The Schistosoma mansoni schistosomula tegument (Smteg) plays an important role in triggering the host immune response and mice immunization with Smteg formulated with Freunds adjuvant or alum + CpG induce partial protection against S. mansoni infection associated with an increased antibody production. In this study, we investigated the role of these antibodies in parasite killing both in vitro and in vivo. We demonstrated that these antibodies were able to bind to the surface of S. mansoni recently transformed schistosomula and that these antibodies significantly increase the percentage of schistosomula killed in vitro by complement activation. Passive transference of immune sera decreased the parasite burden and the number of eggs trapped in the organs of mice that received sera containing anti-Smteg antibodies. These results demonstrate that antibodies specific to surface tegumental antigens are involved in parasite elimination in mice immunized with Smteg