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Infection and Immunity, June 1999, p. 3087-3095, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Increased Antimycobacterial Immunity in Interleukin-10-Deficient Mice

Peter J. Murray,1,2,3,* and Richard A. Young2,3

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-27941; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 021422; and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 021393

Received 26 October 1998/Returned for modification 21 December 1998/Accepted 17 March 1999

Macrophage effector functions are essential for clearing mycobacterial infections. Interleukin 10 (IL-10) negatively regulates macrophages and could be a factor inhibiting effective antimycobacterial immunity. We previously showed that transgenic mice which produce excess IL-10 from T cells are susceptible to infection, even though these mice continue to produce gamma interferon (IFN-gamma ) at levels similar to those in controls. Here, we extend our genetic analysis of the functions of IL-10 in antimycobacterial immunity by testing the hypothesis that IL-10-deficient (IL-10-/-) mice should be more resistant to mycobacteria than control mice. Mycobacterium bovis bacillus Calmette-Guérin-infected IL-10-/- mice had significantly lower bacterial burdens than control mice early in the infection. Contrary to expectations, however, IL-10-/- mice did not have increased levels of IFN-gamma , either from T cells or in the plasma, suggesting that other mechanisms are responsible for the increased resistance. However, macrophages from IL-10-/- mice produced increased levels of inflammatory cytokines, including IFN-gamma , as well as nitric oxide and prostaglandins, which could account for increased antimycobacterial immunity. Our genetic analysis revealed that IL-10 is an inhibitor of early mycobacterial clearance. The data also suggest that IL-10 negatively regulates numerous macrophage functions as well as playing a role in down-regulating the general inflammatory response, especially in conditions where an infection must be controlled through macrophage activity.

* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105-2794. Phone: (901) 495 3219. Fax: (901) 495 3099. E-mail: peter.murray{at}stjude.org.

Infection and Immunity, June 1999, p. 3087-3095, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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