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Liver granuloma; LPS hypersensitivity; NK cells; Propionibacterium acnes; T cells
Abstract:
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-γ production. We show that P. acnes elicits IL-12p40 and p35 mRNA expression in macrophages, and IFN-γ mRNA in liver CD4+ T cells and NK cells. After priming with P. acnes, CD4+ T cells serve as the major IFN-γ mRNA source. In the absence of CD4+ T cells, CD8+ T cells (regardless of antigenic specificity) or NK cells can produce sufficient IFN-γ to induce the P. acnes-driven immune effects. Moreover, in the absence of αβT cells, γδT cells also enable the development of strongly enhanced TNF-α and IFN-γ 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.
