Neutralization or absence of the interleukin-23 pathway does not compromise immunity to mycobacterial infection.
Interleukin-23 (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, in part due to its stimulation of the proinflammatory cytokine IL-17A. It is less clear, however, if IL-23 is required during the immune response to pathogens. We examined the role of IL-23 during Mycobacterium bovis BCG infection. We found that IL-23 reduces the 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 granulomata is not affected 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 in both wild-type and IL-12-deficient mice also has little effect on the 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.
Chackerian
Alissa A
AA
Discovery Research and Experimental Pathology and Pharmacology, Schering-Plough Biopharma, 901 California Ave., Palo Alto, CA 94304-1104, USA.
Chen
Shi-Juan
SJ
Brodie
Scott J
SJ
Mattson
Jeanine D
JD
McClanahan
Terrill K
TK
Kastelein
Robert A
RA
Bowman
Edward P
EP
D000818:Animals; D005260:Female; D006099:Granuloma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D053760:Interleukin-23 Subunit p19 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*
C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D018123:Receptors, Interleukin; D018664:Interleukin-12