Innate, antigen-independent role for T cells in the activation of the immune system by Propionibacterium acnes.
Propionibacterium acnes is a human commensal but also an opportunistic pathogen. In mice, P. acnes exerts strong immunomodulatory activities, including formation of intrahepatic granulomas and induction of LPS hypersensitivity. These activities are dependent on P. acnes recognition via TLR9 and subsequent IL-12-mediated IFN-gamma production. We show that P. acnes elicits IL-12p40 and p35 mRNA expression in macrophages, and IFN-gamma mRNA in liver CD4(+) T cells and NK cells. After priming with P. acnes, CD4(+) T cells serve as the major IFN-gamma mRNA source. In the absence of CD4(+) T cells, CD8(+) T cells (regardless of antigenic specificity) or NK cells can produce sufficient IFN-gamma to induce the P. acnes-driven immune effects. Moreover, in the absence of alpha beta T cells, gamma delta T cells also enable the development of strongly enhanced TNF-alpha and IFN-gamma responses to LPS and intrahepatic granuloma formation. Thus, under microbial pressure, different T-cell types, independent of their antigen specificity, exert NK-cell-like functions, which contribute decisively to the activation of the innate immune system.
Tchaptchet
Sandrine
S
Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Kirberg
Jörg
J
Freudenberg
Nikolaus
N
Schamel
Wolfgang W A
WW
Galanos
Chris
C
Freudenberg
Marina A
MA
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006099:Granuloma / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009894:Opportunistic Infections / Q000276:immunology / Q000382:microbiology; D011425:Propionibacterium acnes / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
D000942:Antigens, Bacterial; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta