Type I interferons drive MAIT cell functions against bacterial pneumonia27 Jul 2023 10:06
Https://rupress.org/jem/article/220/10/e20230037/276132/Type-I-interferons-drive-MAIT-cell-functions
Concluding remarks
Our data identify type I IFNs as key drivers of MAIT cell functions during pulmonary infection with K. pneumoniae. Type I IFNs act on MAIT cells controlling their activation, effector functions, and induction of a Th1/cytotoxic transcriptional program, ultimately contributing to host protection. Thus, during Klebsiella infection, MAIT cells become potent effectors by sensing inflammation independently of cognate antigen. This behavior strongly resembles that of memory CD8+ T cells, whose effector functions (Kohlmeier et al., 2010; Soudja et al., 2012) and trafficking (Sung et al., 2012) can be regulated by type I IFNs in an antigen-independent manner. The cytokine-mediated activation of MAIT cells in response to Klebsiella contrasts with the MR1-dependent activation during infection with other bacteria such as F. tularensis or L. longbeachae (Meierovics et al., 2013; Wang et al., 2018, 2019). The distinct timeframes of the infections (2 d vs. 2 wk) and the different activation/recruitment of immune cells associated with the specific pathogens may contribute to these differences. Accordingly, it is likely that the timing and (local) concentration of type I IFN delivery accompanying different infections will critically regulate subsequent MAIT cell responses. In keeping with this, IFN-β treatment of human naïve T cells induces several temporal transcriptional waves that regulate the dynamics of T cell activation and differentiation (Sumida et al., 2022). Given the abundance of MAIT cells in humans and their rapid response to inflammatory signals, we propose that type I IFNs may serve as a new molecular target to manipulate MAIT cell functions during infections
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