Parasite interactions with dendritic cells and macrophages: Implications for cutaneous Leishmaniasis caused by Leishmania amazonensis

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Title: Parasite interactions with dendritic cells and macrophages: Implications for cutaneous Leishmaniasis caused by Leishmania amazonensis
Author: Hai Qi
Abstract: Protozoan Leishmania is an important human pathogen that affects millions people worldwide . Investigation of experimental Leishmania infection in mice has been instrumental to our understanding of interactions between the parasite and the host immune system . Previous studies have established the model of Th1 -Th2 paradigm : gamma interferon (IFN -g ) -secreting Th1 cells protect the host from developing progressive diseases , while interleukin (IL ) -4 -producing Th2 cells drive the disease pathogenesis . Focused on L . amazonensis infection in mice , this dissertation study is mainly intended to understand the cellular mechanism underlying the generation of parasite -specific Th2 cells and to ascertain the role for IFN -g in parasite -macrophage interactions . We showed that L . amazonensis parasites infected and activated dendritic cells (DCs ) , a population of phagocytic antigen -presenting cells specialized in activating naïve T cells . We found that DCs from susceptible or resistant mice differentially responded to amastigotes in CD40 -dependent cytokine production and that amastigote -infected DCs favor Th2 priming in susceptible but not resistant mice . IFN -g is believed to be crucial for activating macrophages to kill intracellular parasites such as L . major . However , we found that L . amazonensis amastigotes but not promastigotes could not only survive but also replicate better in IFN -g -activated macrophages . The promastigote was evidently killed in IFN -g -activated macrophages . On the other hand , macrophages activated with IFN -g and LPS were able to limit intracellular amastigote replication . When tested in vivo , endogenous IFN -g apparently exerted minimal effects on the course of amastigote infection . It is likely that IFN -g plays a bidirectional role during L . amazonensis infection : when optimally coupled with other factors , it can activate macrophages to control parasite infection ; while in the absence of such synergy , it would promote amastigote propagation by itself . Collectively , results presented in this dissertation have pointed to the unique ability of L . amazonensis amastigotes to modulate host immune system to the advantage of their own survival .
URI: http : / /hdl .handle .net /2152 .3 /94
Date: 2003-03-26

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Parasite interactions with dendritic cells and macrophages: Implications for cutaneous Leishmaniasis caused by Leishmania amazonensis. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /94 .

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