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Leishmaniasis in Latin America: an advanced perspective on immunopatogenetic factors of cutaneous and visceral infection.

Grant number: 19/13880-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2021
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Carlos Eduardo Pereira Corbett
Grantee:André Nicolau Aquime Gonçalves
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/50315-0 - Leishmaniasis in Latin America: an advanced perspective on immunopathogenetic factors of cutaneous and visceral infection, immunomodulators of the sandflies vector saliva and immunogenic exo-antigens of Leishmania (L.) infantum chagasi as vaccine candidates, AP.TEM

Abstract

Human leishmaniases, both the cutaneous or muco-cutaneous forms, as well as the systemic visceral form, remain representing till now, an important public health problem around the world, especially in tropical and subtropical areas of the globe. In this way, Latin America appears as one of most compromised areas by these injuries, where some countries such as Brazil, in the South America, and Panama and Honduras, in the Central America, present an interesting epidemiological feature due to some peculiarities related not only to the antigenic capacity of Leishmania species, as well as the interaction of these parasites with the human immune response, resulting in the immunopatogenetic process that can give rise to the tegumentary leishmaniasis or systemic visceral leishmaniasis. In the case of American cutaneous leishmaniasis (ACL), it has called attention the complexity of the immune biological process involving seven Leishmania species acting as etiologic agents of the disease in Brazil. In Panama, L. (V.) panamensis is considered the main agent of the disease, but there are also other parasites involved with the etiology of ACL, such as L. (L.) amazonensis, L. (L.) mexicana and L. (L.) colombiensis. As a result of this process, five clinical forms of ACL have been observed: localized cutaneous and borderline disseminated cutaneous forms, both caused by any parasite species above mentioned, besides of mucocutaneous or mucosal forms mainly due to L. (V.) panamensis in Panama, and L. (V.) braziliensis in Brazil, and anergic diffuse cutaneous form due to L. (L.) amazonensis in Brazil; however, it should be highlighted that the last two forms represent the clinical forms with the highest pathogenic potential to humans, whose immunopathogenetic basis is one of the major aims of this project that will be investigated in Brazil and Panama by studying the gene expression and in situ phenotypic markers, trying to better understanding the cell signaling factors and the cytokines profiles of innate and adaptive immune responses of the hosts. By the other side, although American visceral leishmaniasis (AVL) represents the clinical manifestation of greatest interest regarding the interaction between L.(L.)i. chagasi and human immune response, there is no doubt that we cannot neglect other clinical-immunological manifestations of the host resulting from this interaction that certainly will contribute for improving the control measures against AVL. Thus, it is of our great interest try to clarify the immunopathogenetic basis that support these sequences of clinical-immunological events, driving to the susceptibility or resistance to the infection, which may support new strategies for the control and treatment of LVA. In Honduras, the epidemiological features of the disease seems more unusual because only one species, L. (L.) i. chagasi, has been incriminated as the agent of American visceral leishmaniasis (AVL) in children, as well as the agent of cutaneous manifestations in adolescents and adults. Thus, the first aim in Honduras is to typify the clinical-immunological spectrum of human L.(L.)i. chagasi infection in those cases of systemic infection besides to evaluate the innate and adaptive immune responses of the individuals, according with their clinical-immunological profile. In those cases with cutaneous manifestation, it will be investigated the immunopathological features in the biopsies of skin lesions submitted to immunohistochemistry for cell surface and intracellular markers, aiming to clarify, on a whole, the immunopathogenetic basis responsible for these two clinical manifestations caused by L. (L.) i. chagasi in Honduras.

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