title: Interleukin-23 restores immunity to Mycobacterium tuberculosis infection in IL-12p40-deficient mice and is not required for the development of IL-17-secreting T cell responses.
abstract: Host control of Mycobacterium tuberculosis is dependent on the activation of CD4+ T cells secreting IFN-gamma and their recruitment to the site of infection. The development of more efficient vaccines against tuberculosis requires detailed understanding of the induction and maintenance of T cell immunity. Cytokines important for the development of cell-mediated immunity include IL-12 and IL-23, which share the p40 subunit and the IL-12Rbeta1 signaling chain. To explore the differential effect of IL-12 and IL-23 during M. tuberculosis infection, we used plasmids expressing IL-23 (p2AIL-23) or IL-12 (p2AIL-12) alone in dendritic cells or macrophages from IL-12p40(-/-) mice. In the absence of the IL-12/IL-23 axis, immunization with a DNA vaccine expressing the M. tuberculosis Ag85B induced a limited Ag-specific T cell response and no control of M. tuberculosis infection. Co-delivery of p2AIL-23 or p2AIL-12 with DNA85B induced strong proliferative and IFN-gamma-secreting T cell responses equivalent to those observed in wild-type mice immunized with DNA85B. This response resulted in partial protection against aerosol M. tuberculosis; however, the protective effect was less than in wild-type mice owing to the requirement for IL-12 or IL-23 for the optimal expansion of IFN-gamma-secreting T cells. Interestingly, bacillus Calmette-Guérin immune T cells generated in the absence of IL-12 or IL-23 were deficient in IFN-gamma production, but exhibited a robust IL-17 secretion associated with a degree of protection against pulmonary infection. Therefore, exogenous IL-23 can complement IL-12 deficiency for the initial expansion of Ag-specific T cells and is not essential for the development of potentially protective IL-17-secreting T cells.
authors.affiliation: Mycobacterial Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Wozniak
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Ryan
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D007109:Immunity; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology* / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000628:therapy; D019444:Vaccines, DNA
chemical_list: D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D019444:Vaccines, DNA