Figure 2.

IL-27 in experimental TB and its protective and pathological immune responses at different states of Mtb infection. IL-27, produced by DC or MΦ in response to infection with Mtb, acts on various cell types. It controls the accumulation of PD1⁺ CD4 T cells in the lung parenchyma and limits the expansion of IL-17A-producing Th17 cells either directly or indirectly by increasing the numbers of T_reg or inhibiting the production of the Th17-driving cytokines IL-6 and IL-23 by DC and Mϕ. Thereby, defending mechanisms as infiltration of the lung tissue with PD⁺ CD4⁺ T cells, the chemokine-mediated formation of protective granulomas, the recruitment of B cells and IFNγ/TNF/IL-2-producing multifunctional (Muf) T cells as well as subsequent MΦ activation are diminished by IL-27. However, even if IL-27 suppresses these protective functions, during later states of infection it also controls lung-specific advanced inflammatory cell infiltration and interstitial collagen deposition but additionally systemic cytokine levels and eventually premature death.