title: The role of IL-4 and IL-13 in cutaneous Leishmaniasis.
abstract: Murine models of Leishmania major infection in the 1980s revealed two distinct, counter-regulatory populations of CD4(+) T helper (Th) cells, delineated Th1 and Th2, and their archetypal cytokines, interferon gamma (IFN-γ) and interleukin (IL)-4/IL-13, which promoted resistance/susceptibility to infection, respectively. However, the introduction of global cytokine-deficient mice in the 1990s revealed pleiotropic immune-regulatory mechanisms of IL-4 and IL-13 that either controlled or exacerbated disease. This undermined the basic premise that IL-4/IL-13 played paramount roles in facilitating a non-healing Th2 response to Leishmania infection and instead suggested that both IL-4 and IL-13-dependent and IL-4/IL-13-independent factors orchestrate disease outcome. The recent characterization of cell-type specific IL-4Rα deficient mice was initiated to help reconcile these observations and dissect the cell-specific effects of IL-4/IL-13 during infection. In this review, we summarize original and recent findings with regard to the role of IL-4 and IL-13 in cutaneous Leishmaniasis. Using the information discerned from various studies and our conditional IL-4Rα gene-deficient mice, we particularly discuss the double-edged sword IL-4 (and in some Leishmania disease models IL-13) in driving a susceptible Th2 response, their immune cell targets that support healing or non-healing responses and their novel role in mediating a Th1 response during disease.
authors.affiliation: International Center for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component and Institute of Infectious Diseases and Molecular Medicine (IIDMM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors.forename: Ramona
authors.initials: R
authors.lastname: Hurdayal
authors.affiliation: International Center for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component and Institute of Infectious Diseases and Molecular Medicine (IIDMM), Division of Immunology, University of Cape Town, Cape Town, South Africa. Electronic address: brombacherfrank@gmail.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D015847:Interleukin-4
keywords: Cutaneous Leishmaniasis; Gene-deficient mouse models; IL-13; IL-4; IL-4Rα