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Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/6115

Title: Modulation of macrophage/lymphocyte interactions during leishmania infection
Authors: Diaz, Suraya Alexandra das Neves Guevara, 1981-
Advisor: Gomes, Gabriela Santos
Keywords: Leishmania Infantum
Macrófagos
Linfócitos
Citocinas
Cães
Teses de mestrado - 2009
Issue Date: 2009
Abstract: Leishmania is an obligate intracellular protozoan that causes a variety of diseases in mammals including humans in tropics and subtropics areas. The parasite alternates between sand fly and mammalian hosts in two developmental forms, the promastigote and the amastigote respectively. The diverse clinical manifestations depend upon the Leishmania species, Leishmania strain virulence and on the immune response of the host. This disease ranges from a self healing cutaneous Leishmaniosis to a lethal visceral form. Infected dogs are the main domestic reservoir of these parasites and represent an epidemiological risk for the transmission to humans. The strategies used to prevent Leishmaniosis are not totally effective thus Leishmaniosis control remains a partially unsolved problem. In this way preventing zoonotic visceral Leishmaniosis could be achieved through dog vaccination. When Leishmania parasite is inoculated within the vertebrate host dermis, it could be lysed by complement or destructed by phagocytes. Although Leishmania successfully evade and resist to non-specific defence mechanisms such as complement mediated lysis, to ultimately enhance the binding and entering into mononuclear phagocytes, the host cells in which it replicates. Leishmania amastigotes reside and proliferate in macrophage phagolysosomes. Monocyte/macrophages if activated by IFN-γ are able to present parasite antigens via MHC class II molecules, playing an important role as effector cells for the destruction of intracellular Leishmania parasites. In addition, the balance between IL-10 and IL-12, the associated level of IFN-γ production and macrophage activation is likely to play a critical role in the parasite burden levels. The murine model of L. major infection indicates that the outcome of the infection is largely determined by expansion of the different subsets of CD4+ Th cells. In resistant mice the development of protective immunity and an expansion of CD4+ T cells producing IFN-γ are observed whereas in susceptible mice the immune response is characterised by the expansion of CD4+ T cells producing IL-4 and IL-10 which downregulate Th1-associated activities. The understanding of the immunological mechanisms involved in resistance/susceptibility to infection by Leishmania is fundamental for the development of immunoprophylatic tools. Therefore the aim of this study is to evaluate in vitro modulation of macrophage/lymphocyte activation by quantification of the expression of MHC class II at macrophage surface with flow cytometry and quantification of CD80, CD86, IL-12, CD28, CTLA-4 and IFN-γ with real time PCR. The results showed a upregulation of MHC class II during in vitro L. infantum infection. Also, a possible lack of coordinate costimulator expression was found, which may lead to subsequent loss of T cell function. These results are in agreement with bibliography and constitute a new contribution for canine host and Leishmania parasite interaction understanding.
Description: Tese de mestrado, Medicina (Microbiologia Clínica), Faculdade de Medicina, Universidade de Lisboa, 2009
Peer Reviewed: yes
URI: http://hdl.handle.net/10451/6115
Appears in Collections:FM - Dissertações de Mestrado

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