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Infection and Immunity, February 2001, p. 906-911, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.906-911.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection

Abhay R. Satoskar,* Marcelo Bozza, Miriam Rodriguez Sosa, Guoshing Lin, and John R. David

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Masschusetts 02115

Received 9 May 2000/Returned for modification 10 July 2000/Accepted 10 November 2000

To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF-/-) and wild-type (MIF+/+) mice. Following cutaneous L. major infection, MIF-/- mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF+/+ mice. Interestingly, antigen-stimulated lymph node cells from MIF-/- mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-gamma ) than those from MIF+/+ mice, although the differences were statistically not significant. IFN-gamma -activated resting peritoneal macrophages from MIF-/- mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF-/- mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. major in vivo. Furthermore, they indicate that the susceptibility of MIF-/- mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

* Corresponding author. Mailing address: Dept. of Immunology and Infectious Diseases, Harvard School of Public Health, Bldg. 1, Rm. 804, 665 Huntington Avenue, Boston, MA 02115. Phone: (617) 432-4884. Fax: (617) 738-4914. E-mail: asatoska{at}hsph.harvard.edu.

Infection and Immunity, February 2001, p. 906-911, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.906-911.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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