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Infect. Immun. doi:10.1128/IAI.00621-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Neutralization or absence of the IL-23 pathway does not compromise immunity to mycobacterial infection

Discovery Research, Experimental Pathology and Pharmacology, Schering-Plough Biopharma (formerly DNAX Research, Inc), 901 California Ave, Palo Alto, CA 94304-1104, USA. Department of Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, NJ, 07848, USA.

^* To whom correspondence should be addressed. Email: eddie.bowman{at}spcorp.com.

	Abstract

IL-23, a member of the IL-12 family, is a heterodimeric cytokine that is composed of the p40 subunit of IL-12 plus a unique p19 subunit. IL-23 is critical for autoimmune inflammation, partially by its stimulation of the pro-inflammatory cytokine IL-17A. It is less clear, however, if IL-23 is required during the immune response to pathogens. We have examined the role of IL-23 during Mycobacterium bovis BCG infection. We find that IL-23 reduces bacterial burden and promotes granuloma formation when IL-12 is absent. However, IL-23 does not contribute substantially to host resistance when IL-12 is present, as the ability to control bacterial growth and form granulomas is unaffected in IL-23p19-deficient mice and mice treated with a specific anti-IL-23p19 antibody. IL-23p19-deficient mice are also able to mount an effective memory response to secondary infection with BCG. While IL-23p19-deficient mice do not produce IL-17A, this cytokine is not necessary for effective control of infection, and antibody-blocking of IL-17A both in wild-type and IL-12-deficient mice also has little effect on bacterial burden. These data suggest that IL-23 by itself does not play an essential role in the protective immune response to BCG infection; however, the presence of IL-23 can partially compensate for the absence of IL-12. Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection.

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