Abstract
BackgroundLeishmania parasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation. Experimental Leishmania infection in mice has been widely used in the identification of specific parasite virulence factors involved in the interaction with the host immune system. Cysteine-proteinase B (CPB) is an important virulence factor in parasites from the Leishmania (Leishmania) mexicana complex: it inhibits lymphocytes Th1 and/or promotes Th2 responses either through proteolytic activity or through epitopes derived from its COOH-terminal extension. In the present study we analyzed the effects of Leishmania (Leishmania) amazonensis CPB COOH-terminal extension-derived peptides on cell cultures from murine strains with distinct levels of susceptibility to infection: BALB/c, highly susceptible, and CBA, mildly resistant.ResultsPredicted epitopes, obtained by in silico mapping, displayed the ability to induce cell proliferation and expression of cytokines related to Th1 and Th2 responses. Furthermore, we applied in silico simulations to investigate how the MHC/epitopes interactions could be related to the immunomodulatory effects on cytokines, finding evidence that specific interaction patterns can be related to in vitro activities.ConclusionsBased on our results, we consider that some peptides from the CPB COOH-terminal extension may influence host immune responses in the murine infection, thus helping Leishmania survival.
Highlights
Leishmania parasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation
In this system, the outcome of infection is determined by the balance between these two types of response [7]. This dichotomy is not so clearly observed in murine infections caused by the Leishmania (Leishmania) mexicana complex species, as L. (L.) amazonensis, where the susceptibility of the host to the infection seems to be associated with an insufficient Th1 response rather than a dominant Th2 response [8]
Sequencing of the L. (L.) amazonensis Cysteine-proteinase B (CPB) COOH-terminal extension L. (L.) amazonensis CPB COOH-terminal extension encoding genome sequence was amplified and cloned using primers previously produced for an analogous region of L. (L.) pifanoi CPB
Summary
Leishmania parasites have been reported to interfere and even subvert their host immune responses to enhance their chances of survival and proliferation. In the present study we analyzed the effects of Leishmania (Leishmania) amazonensis CPB COOH-terminal extension-derived peptides on cell cultures from murine strains with distinct levels of susceptibility to infection: BALB/c, highly susceptible, and CBA, mildly resistant. Amastigote forms of Leishmania are intracellular parasites, inhabiting preferentially cells of the mononuclear phagocyte system, and present a series of adaptive peculiarities in this phase of the biological cycle These adaptations allow the parasites to escape or interfere with the host immune responses and, maintain the infection. In the murine Leishmania (Leishmania) major infection model it has been established that a T-helper cell type 1 (Th1) immune response is effective against the parasites, while a Th2 response may lead to disease exacerbation In this system, the outcome of infection is determined by the balance between these two types of response [7]. Regulatory cytokines, as IL-10, might influence the outcome of the infection in a manner not directly linked to the Th1/Th2 dichotomy [9]
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