Salmonella co-opts the host's innate immune system to regulate its flagellin and conceal itself

What is it about?

While the effect of bacterial molecules on the host immune system is well studied, how host factors affect the expression of bacterial molecules is less appreciated. In this study, we uncover the impact of inflammasome activation and type 1 interferon on the expression of bacterial flagellin. Flagellin induces NLRC4 inflammasome-mediated death of macrophages causing clearance of Salmonella. We show that inflammasome activation also produces lysophospholipids which increase flagellin expression by Salmonella early in infection. We further demonstrate that as infection progresses, type 1 IFN inhibits NLRC4 and lysophospholipid synthesis, resulting in down-regulation of flagellin expression, a phenotype that the pathogen switches to during establishment of in vivo infection. These findings unravel pathways for biphasic regulation of expression of flagellin, a key Salmonella effector.

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Why is it important?

This work highlights how host factors impact the expression of bacterial molecules and shape host-pathogen crosstalk. It also emphasizes the need to fully understand how bacterial pathogens have evolved to adapt to and benefit from certain aspects of the host immune response (e.g. type 1 interferons). Future work in this area will be helpful in developing host-directed immunotherapies which can pave the way forward in tackling antimicrobial resistance in the context of bacterial infections. Because the production of type 1 interferons is a bonafide response to virus infections, the interferon-dependent response that Salmonella co-opts to reduce its flagellin and avoid recognition by the immune system may provide one explanation for why people are more prone to secondary bacterial infections after enduring a primary viral infection.

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