Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis.
The outcomes of Leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. While subclinical infection and self-healing cutaneous leishmaniasis (CL) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (VL). It is known that infection control requires Th1-differentiation cytokines (IL-12, IL-18, and IL-27) and Th1 cell and macrophage activation. However, there is no generalized consensus for the mechanisms of host susceptibility. The recent studies on regulatory T cells and IL-17-producing cells help explain the effector T cell responses that occur independently of the known Th1/Th2 cell signaling pathways. This review focuses on the immunopathogenesis of non-healing American CL and progressive VL. We summarize recent evidence from human and animal studies that reveals the mechanisms of dysregulated, hyper-responses to Leishmania braziliensis, as well as the presence of disease-promoting or the absence of protective responses to Leishmania amazonensis and Leishmania donovani. We highlight immune-mediated parasite growth and immunopathogenesis, with an emphasis on the putative roles of IL-17 and its related cytokines as well as arginase. A better understanding of the quality and regulation of innate immunity and T cell responses triggered by Leishmania will aid in the rational control of pathology and the infection.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA. lysoong@utmb.edu
Lynn
L
Soong
Calvin A
CA
Henard
Peter C
PC
Melby
D000818:Animals; D060085:Coinfection; D006224:Cricetinae; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007891:Leishmania / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines