Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative diseases. Recent studies show that in response to certain environmental toxins and endogenous proteins, microglia can enter an overactivated state and release reactive oxygen species (ROS) that cause neurotoxicity. Pattern recognition receptors expressed on the microglial surface seem to be one of the primary, common pathways by which diverse toxin signals are transduced into ROS production. Overactivated microglia can be detected using imaging techniques and therefore this knowledge offers an opportunity not only for early diagnosis but, importantly, for the development of targeted anti-inflammatory therapies that might slow or halt the progression of neurodegenerative disease.

Microglia-mediated neurotoxicity: uncovering the molecular mechanisms

Circulating blood monocytes supply peripheral tissues with macrophage and dendritic cell (DC) precursors and, in the setting of infection, also contribute directly to immune defense against microbial pathogens. In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractant protein (MCP)-1 (CCL2) secretion. In murine models, CCR2-mediated monocyte recruitment is essential for defense against Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans infection, implicating inflammatory monocytes in defense against bacterial, protozoal, and fungal pathogens. Recent studies indicate that inflammatory monocyte recruitment to sites of infection is complex, involving CCR2-mediated emigration of monocytes from the bone marrow into the bloodstream, followed by trafficking into infected tissues. The in vivo mechanisms that promote chemokine secretion, monocyte differentiation and trafficking, and finally monocyte-mediated microbial killing remain active and important areas of investigation.

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Monocyte-Mediated Defense Against Microbial Pathogens

Trichomonas vaginalis, a parasitic protozoan, is the etiologic agent of trichomoniasis, a sexually transmitted disease (STD) of worldwide importance. Trichomoniasis is the most common nonviral STD, and it is associated with many perinatal complications, male and female genitourinary tract infections, and an increased incidence of HIV transmission. Diagnosis is difficult, since the symptoms of trichomoniasis mimic those of other STDs and detection methods lack precision. Although current treatment protocols involving nitroimidazoles are curative, metronidazole resistance is on the rise, outlining the need for research into alternative antibiotics. Vaccine development has been limited by a lack of understanding of the role of the host immune response to T. vaginalis infection. The lack of a good animal model has made it difficult to conduct standardized studies in drug and vaccine development and pathogenesis. Current work on pathogenesis has focused on the host-parasite relationship, in particular the initial events required to establish infection. These studies have illustrated that the pathogenesis of T. vaginalis is indeed very complex and involves adhesion, hemolysis, and soluble factors such as cysteine proteinases and cell-detaching factor. T. vaginalis interaction with the members of the resident vaginal flora, an advanced immune evasion strategy, and certain stress responses enable the organism to survive in its changing environment. Clearly, further research and collaboration will help elucidate these pathogenic mechanisms, and with better knowledge will come improved disease control.

Clinical and Microbiological Aspects of Trichomonas vaginalis

In this article, literature records of argasid and ixodid ticks feeding on humans worldwide are provided in view of increased awareness of risks associated with tick bites. Ticks can cause paralyses, toxicoses, allergic reactions and are vectors of a broad range of viral, rickettsial, bacterial and protozoan pathogens. Approximately 12 argasid species (Argas and Ornithodos) are frequently found attached to humans who intrude into tick-infested caves and burrows. Over 20 ixodid tick species are often found on humans exposed to infested vegetation: four of these are Amblyomma species, 7 Dermacentor spp., 3 Haemaphysalis spp., 2 Hyalomma spp. and 6 Ixodes species. Personal protection methods, such as repellents and acaricide-impregnated clothing are advised to minimize contact with infected ticks. Acaricidal control of ixodid ticks is impractical because of their wide distribution in forested areas, but houses infested with soft ticks can be sprayed with acaricidal formulations. Attached ticks should be removed without delay. The best way is to grasp the tick as close to the skin as possible with fine tweezers and pull firmly and steadily without twisting. Finally, despite the fact that most people who are bitten destroy the offending tick in disgust, it is recommended that they preserve specimens in ethanol for taxonomic identification and detection of pathogens by molecular methods.

Ticks feeding on humans: a review of records on human-biting Ixodoidea with special reference to pathogen transmission.

Background: Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study: The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings: Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p,0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions: The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.

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Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

The extracellular tissue penetrating protozoan parasite Entamoeba histolytica has been known to induce host cell apoptosis. However, the intracellular signaling mechanism used by the parasite to trigger apoptosis is poorly understood. In this study, we investigated the roles of reactive oxygen species (ROS), and of MAPKs in the Entamoeba-induced apoptosis of human neutrophils. The neutrophils incubated with live trophozoites of E. histolytica revealed a marked increase of receptor shedding of CD16 as well as phosphatidylserine (PS) externalization on the cell surface. The Entamoeba-induced apoptosis was effectively blocked by pretreatment of cells with diphenyleneiodonium chloride (DPI), a flavoprotein inhibitor of NADPH oxidase. A large amount of intracellular ROS was detected after exposure to viable trophozoites, and the treatment with DPI strongly inhibited the Entamoeba-induced ROS generation. However, a mitochondrial inhibitor rotenone did not attenuate the Entamoeba-induced ROS generation and apoptosis. Although E. histolytica strongly induced activation of ERK1/2 and p38 MAPK in neutrophils, the activation of ERK1/2 was closely associated with ROS-mediated apoptosis. Pretreatment of neutrophils with MEK1 inhibitor PD98059, but not p38 MAPK inhibitor SB202190, prevented Entamoeba-induced apoptosis. Moreover, DPI almost completely inhibited Entamoeba-induced phosphorylation of ERK1/2, but not phosphorylation of p38 MAPK. These results strongly suggest that NADPH oxidase-derived ROS-mediated activation of ERK1/2 is required for the Entamoeba-induced neutrophil apoptosis.

https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/147547/1/T200500301.pdf

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

Neutrophils are the predominant inflammatory cells found in the vaginal discharges of patients infected with Trichomonas vaginalis. Although chemoattractants, such as leukotriene B4 and interleukin-8 (IL-8), are found in the vaginal discharges of symptomatic trichomoniasis patients, little is known about the mechanism of how neutrophils accumulate or mediate initial inflammatory response after acute T. vaginalis infection. We examined IL-8 production in neutrophils activated by T. vaginalis and evaluated the factors involved in T. vaginalis adherence that might affect IL-8 production. When human neutrophils were stimulated with live trophozoites, T. vaginalis lysate, or T. vaginalis excretory-secretory products, the live trichomonads induced higher levels of IL-8 production than the lysate or products did. When live trichomonads were pretreated with various inhibitors of proteinase, microtubule, microfilament, or adhesin (which are all known to participate in the adherence of T. vaginalis to vaginal epithelial cells), IL-8 production significantly decreased compared with the untreated controls. Furthermore, an NF-κB inhibitor (pyrrolidine dithiocarbamate), a mitogen-activated protein (MAP) kinase (MEK) inhibitor (PD98059), and a p38 MAP kinase inhibitor (SB203580) significantly suppressed IL-8 synthesis in neutrophils. These results suggest that live T. vaginalis, particularly adherent trophozoites, can induce IL-8 production in neutrophils and that this action may be mediated through the NF-κB and MAP kinase signaling pathways. In other words, T. vaginalis-induced neutrophil recruitment may be mediated via the IL-8 expressed by neutrophils in response to activation by live T. vaginalis.

https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/112530/1/T200401250.pdf

Production of interleukin-8 by human neutrophils stimulated with Trichomonas vaginalis

Eosinophilic leukocytes function in host protection against parasitic worms. In turn, helminthic parasites harbor specific molecules to evade or paralyze eosinophil-associated host immune responses; these molecules facilitate the migration and survival of parasitic helminths in vivo. This competition between eosinophil and worm leads to stable equilibria between them. An understanding of such dynamic host-eosinophil interactions will help us to uncover mechanisms of cross talk between host and parasite in helminth infection. In this review, we examine recent findings regarding the innate immune responses of eosinophils to helminthic parasites, and discuss the implications of these findings in terms of eosinophil-mediated tissue inflammation in helminth infection.

Eosinophil-Mediated Tissue Inflammatory Responses in Helminth Infection

Epidemiological surveys concerning cestodes of medical importance in Korea have been sporadically reported by many workers. Among various parasitic infections, cestode infections occur less frequently than other helminthiases, but they often cause serious clinical complications. Cestodes reported so far in Korea belong to the Order Pseudophyllidea or Cyclophyllidea (Subclass Cestoda), i.e., Diphyllobothrium latum, D. yonagoense, Spirometra erinacei, sparganum, Hymenolepis diminuta, H. nana, Mesocestoides lineatus, Taenia saginata, T. solium, metacestode of T. solium (cysticercus), and Echinococcus granulosus. The present paper is a brief review of the literature concerning these cestode infections in Korea. Taeniases by T. saginata or T. solium are prevalent cestode infections in Korea, and cysticercosis by T. solium often reveals serious clinical manifestations. H. nana infection is relatively rare, showing 0.22% egg positive rate in a nationwide survey in 1986. Sparganosis by the plerocercoid larva of Spirometra is not an uncommon cestode infection in man, and 16 kinds of animal hosts including the snakes and frogs have been reported. D. latum infection has been an uncommon intestinal parasitosis, but it tends to increase nowadays. Most of human hydatidosis cases have been recognized as imported ones from outside Korea, but one case was proven indigenous. Other 4 kinds of cestodiases are extremely rare in Korea and only a few cases have been recorded.

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Cestode infections in Korea.

The role of iron was evaluated with respect to the virulence of Trichomonas vaginalis in mice. Iron-supplemented and iron-depleted Diamond's trypticase–yeast extract–maltose (TYM) media were prepared by adding 360 µM of ferrous sulfate and 100 µM of 2,2′-dipyridyl. Trophozoites cultivated from normal TYM and iron-supplemented TYM media produced subcutaneous abscesses; however, trichomonads grown in an iron-deficient TYM medium failed to produce any pathology. In addition to the increased virulence of trophozoites in mice, iron affects the level of adherence and the cytotoxicity of trichomonads to HeLa cells, which are significantly reduced in trophozoites grown in iron-deficient medium. In conclusion, it is suggested that under iron-depleted conditions such as that induced by 2,2′-dipyridyl the virulence of T. vaginalis is reduced.

Duk-Young Min

Papers

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

Production of interleukin-8 by human neutrophils stimulated with Trichomonas vaginalis

Eosinophil-Mediated Tissue Inflammatory Responses in Helminth Infection

Cestode infections in Korea.

Effect of Iron on the Virulence of Trichomonas vaginalis