Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present.
Recent evidence suggests that absence of the IL-12p40 subunit is more detrimental to the generation of protective responses than is the absence of the p35 subunit. To determine whether this is the case in tuberculosis, both p35 and p40 knockout mice were infected with Mycobacterium tuberculosis. Mice lacking the p40 subunit were highly susceptible to increased bacterial growth, exhibited reduced production of IFN-gamma, and had increased mortality. In contrast, mice lacking the p35 subunit exhibited a moderate ability to control bacterial growth, were able to generate Ag-specific IFN-gamma responses, and survived infection longer. The superior Ag-specific responses of the p35 gene-disrupted mice, when compared with the p40 gene-disrupted mice, suggest that the p40 subunit may act other than as a component of IL-12. A candidate molecule capable of driving the protective responses in the p35 gene-disrupted mice is the novel cytokine IL-23. This cytokine is composed of the IL-12 p40 subunit and a p19 subunit. In support of a role for this cytokine in protective responses to M. tuberculosis, we determined that the p19 subunit is induced in the lungs of infected mice.
Cooper
Andrea M
AM
Mycobacteria Research Laboratories, Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA. acooper@trudeauinstitute.org
Kipnis
Andre
A
Turner
Joanne
J
Magram
Jeanne
J
Ferrante
Jessica
J
Orme
Ian M
IM
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000939:Epitopes; C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018664:Interleukin-12; D007371:Interferon-gamma