Canine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a systemic disease, which can present with variable clinical signs, and clinicopathological abnormalities. Clinical manifestations can range from subclinical infection to very severe systemic disease. Leishmaniosis is categorized as a neglected tropical disease and the complex immune responses associated with Leishmania species makes therapeutic treatments and vaccine development challenging for both dogs and humans. In this review, we summarize innate and adaptive immune responses associated with L. infantum infection in dogs, and we discuss the problems associated with the disease as well as potential solutions and the future direction of required research to help control the parasite.

/pdf/insights-on-adaptive-and-innate-immunity-in-canine-3v5kuymilj.pdf

Insights on adaptive and innate immunity in canine leishmaniosis.

Canine leishmaniosis (CanL) is a vector-borne disease caused by the protozoan Leishmania (Leishmania) infantum species [syn. L. (L.) infantum chagasi species in the Americas] which is transmitted by the bite of a female phlebotomine sand fly. This parasitosis is endemic and affect millions of dogs in Asia, the Americas and the Mediterranean basin. Domestic dogs are the main hosts and the main reservoir hosts for human zoonotic leishmaniosis. The outcome of infection is a consequence of intricate interactions between the protozoan and the immunological and genetic background of the host. Clinical manifestations can range from subclinical infection to very severe disease. Early detection of infected dogs, their close surveillance and treatment are essential to control the dissemination of the parasite among other dogs, being also a pivotal element for the control of human zoonotic leishmaniosis. Hence, the identification of biomarkers for the confirmation of Leishmania infection, disease and determination of an appropriate treatment would represent an important tool to assist clinicians in diagnosis, monitoring and in giving a realistic prognosis to subclinical infected and sick dogs. Here, we review the recent advances in the identification of Leishmania infantum biomarkers, focusing on those related to parasite exposure, susceptibility to infection and disease development. Markers related to the pathogenesis of the disease and to monitoring the evolution of leishmaniosis and treatment outcome are also summarized. Data emphasizes the complexity of parasite-host interactions and that a single biomarker cannot be used alone for CanL diagnosis or prognosis. Nevertheless, results are encouraging and future research to explore the potential clinical application of biomarkers is warranted.

/pdf/biomarkers-associated-with-leishmania-infantum-exposure-1xwiufao6v.pdf

Biomarkers Associated With Leishmania infantum Exposure, Infection, and Disease in Dogs.

Leishmania is a genus of protozoan parasites that give rise to a range of diseases called Leishmaniasis that affects annually an estimated 1.3 million people from 88 countries. Leishmania donovani and Leishmania (L.) infantum chagasi are responsible to cause the visceral leishmaniasis. The parasite can use assorted strategies to interfere with the host homeostasis to establish persistent infections that without treatment can be lethal. In this review, we highlight the mechanisms involved in the parasite subversion of the host protective immune response and how alterations of host tissue physiology and vascular remodeling during VL could affect the organ-specific immunity against Leishmania parasites.

https://www.arca.fiocruz.br/bitstream/icict/16250/2/Freitas%20EO%20The%20contribution%20of%20immune....pdf

The Contribution of Immune Evasive Mechanisms to Parasite Persistence in Visceral Leishmaniasis.

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis

The spleen is a secondary lymphoid organ responsible for immune surveillance against blood-circulating pathogens. Absence of the spleen is associated with increased susceptibility to systemic spread and fatal infection by different pathogens. Severe forms of visceral leishmaniasis are associated with disorganization of spleen compartments where cell interactions essential for splenic immunological function take place. White pulp atrophies, secondary lymphoid follicles and marginal zones vanish, and the boundaries separating white and red pulp blur. Leukocyte populations are reduced or disappear or are replaced by plasma cells. In this paper, we review the published data on spleen disorganization in severe forms of visceral leishmaniasis and propose a histological classification to help the exchange of information among research groups.

/pdf/histological-disorganization-of-spleen-compartments-and-5ejd58h19q.pdf

Histological Disorganization of Spleen Compartments and Severe Visceral Leishmaniasis.

Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L infantum in zoonotic VL Infected dogs develop progressive disease with a large clinical spectrum A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42) When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ TNF showed the best negative correlation (r2 = 0231; p<0001) Herein we describe impairment on mRNA cytokine expression in leishmania infected dogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome

https://www.arca.fiocruz.br/bitstream/icict/14006/2/amanda_cavalcanti_etal_IOC_2015.PDF

Gustavo Leandro Mestre

Papers

Parasite load induces progressive spleen architecture breakage and impairs cytokine mRNA expression in Leishmania infantum-naturally infected dogs.