Leishmaniasis is an important human and animal disease with a worldwide distribution including in North America where endogenous transmission in wild dogs has recently been reported. The disease presents as a spectrum of manifestations that can involve the skin and multiple visceral organs. It is chronic and exhibits a tendency for spontaneous remission. Immunological studies of infections by these parasites have provided valuable insights into functional T cell development in response to antigen activation. It is however intriguing that even though vigorous host immune responses are elicited in response to the parasite, Leishmania persist in the infected host. This suggests that the these parasites have evolved a strategy to evade immune detection.This study proposes that Leishmania amastigotes impair the ability of infected macrophages to process and present parasite molecules to CD4+ T cells. The approach to elucidate the underlying mechanism of this process builds on observations that implicated the phagocytic receptor as a determinant of pathogenesis in the L. mexicana model. Specifically, studies ascertain the evolution of the contents of the parasitophorous vacuole when parasites are internalized through the Fc or complement receptors. The prevailing vacuole characteristerics that exist when the vacuole is permissive of antigen presentation should be readily discerned. These studies will expose parasite processes that can be targeted for the control of Leishmania
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| Ruhland, Aaron; Kima, Peter E (2009) Activation of PI3K/Akt signaling has a dominant negative effect on IL-12 production by macrophages infected with Leishmania amazonensis promastigotes. Exp Parasitol 122:28-36 |
| Kima, Peter E (2007) The amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection and persist. Int J Parasitol 37:1087-96 |
| Kima, Peter E; Dunn, Waltraud (2005) Exploiting calnexin expression on phagosomes to isolate Leishmania parasitophorous vacuoles. Microb Pathog 38:139-45 |
| Pham, Nam-Kha; Mouriz, Jennifer; Kima, Peter E (2005) Leishmania pifanoi amastigotes avoid macrophage production of superoxide by inducing heme degradation. Infect Immun 73:8322-33 |
