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Review
. 2012 Nov;34(6):735-51.
doi: 10.1007/s00281-012-0350-8. Epub 2012 Oct 11.

Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

Lynn Soong  1 , Calvin A Henard, Peter C Melby
Affiliations
Review

Immunopathogenesis of non-healing American cutaneous leishmaniasis and progressive visceral leishmaniasis

Lynn Soong et al. Semin Immunopathol. 2012 Nov.

Abstract

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.

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Figures

Fig. 1
Fig. 1
The complex factors for the regulation of healing and non-healing leishmaniasis
Fig. 2
Fig. 2
Differential responses of Leishmania amazonensis (La) and Leishmania braziliensis (Lb). a Kinetics of NO-mediated killing of La and Lb parasites. CFSE-labeled promastigotes (Pm) and axenic amastigotes (Am, 1 × 107/ml) were exposed to 10 mM NaNO2 in PBS pH 4.5 at 23 °C. The intensity of CFSE was determined by flow cytometry. For untreated parasites, only the 90-min data are shown. b Bone marrow-derived DCs were generated from C57BL/6 mice and infected with promastigotes and axenic amastigotes of La and Lb at the indicated ratios. At 24 h post-infection, the levels of IL-12p40 in culture supernatants were assayed by ELISA. c DC (infected for 24 h) were co-cultured with naïve CD4+ T cells (2 × 106/ml) at an 1:10 DC-to-T ratio for 4 days. The levels of cytokines in culture supernatants were assayed by ELISA. *p<0.05; **p<0.01; ***p< 0.001. b and c were adapted from Vargas-Inchaustegui et al. [65]
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References

    1. Banuls AL, Hide M, Prugnolle F. Leishmania and the leishmaniases: a parasite genetic update and advances in taxonomy, epidemiology and pathogenicity in humans. Adv Parasitol. 2007;64:1–109. - PubMed
    1. Guerra JA, Coelho LI, Pereira FR, Siqueira AM, Ribeiro RL, et al. American tegumentary leishmaniasis and HIV-AIDS association in a tertiary care center in the Brazilian Amazon. AmJTrop Med Hyg. 2011;85:524–527. - PMC - PubMed
    1. Alvar J, Aparicio P, Aseffa A, Den Boer M, Canavate C, et al. The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev. 2008;21:334–359. table of contents. - PMC - PubMed
    1. Lodge R, Ouellet M, Barat C, Andreani G, Kumar P, et al. HIV-1 promotes intake of Leishmania parasites by enhancing phosphatidylserine-mediated, CD91/LRP-1-dependent phagocytosis in human macrophages. PLoS One. 2012;7:e32761. - PMC - PubMed
    1. Tacchini-Cottier F, Weinkopff T, Launois P. Does T helper differentation correlate with resistance or susceptibility to infection with L. major? Some insights form the murine model. Frontiers Immunol. 2012;3:1–9. - PMC - PubMed

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