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Infection and Immunity, April 2005, p. 2101-2108, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2101-2108.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interleukin 10- and Fc{gamma} Receptor-Deficient Mice Resolve Leishmania mexicana Lesions

Laurence U. Buxbaum1,2 and Phillip Scott3*

VA Medical Center,1 Department of Medicine, Division of Infectious Diseases, School of Medicine,2 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania3

Received 25 August 2004/ Returned for modification 11 October 2004/ Accepted 14 December 2004

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 FcR{gamma}–/– 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 Fc{gamma}R leads to resolution of L. mexicana disease and support a model in which ligation of Fc{gamma}R by L. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.

* Corresponding author. Mailing address: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 216 ROS, 3800 Spruce Street, Philadelphia, PA 19104. Phone: (215) 898-1602. Fax: (215) 573-7023. E-mail: pscott{at}vet.upenn.edu.

Editor: J. F. Urban, Jr.

Infection and Immunity, April 2005, p. 2101-2108, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2101-2108.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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