Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania mexicana lesions.
Infection of C57BL/6 (B6) mice with Leishmania mexicana is associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10-/- (IL-10-/-) mice resolve their lesions and exhibit increased gamma interferon (IFN-gamma), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment of L. mexicana-infected IL-10-/- mice with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-opsonized L. mexicana induced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fc receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcRgamma-/- mice resolve L. mexicana lesions, and lymph node cells from these mice produced less IL-10 and more IFN-gamma than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or FcgammaR leads to resolution of L. mexicana disease and support a model in which ligation of FcgammaR by L. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.
Buxbaum
Laurence U
LU
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 216 ROS, 3800 Spruce Street, Philadelphia, PA 19104, USA.
Scott
Phillip
P
D000818:Animals; D002908:Chronic Disease; D007074:Immunoglobulin G / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D053762:Interleukin-12 Subunit p40; D007894:Leishmania mexicana; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D021122:Protein Subunits / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology*
D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D017452:Receptors, IgG; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide