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Preprints, Working Papers, ... (Preprint) Year : 2022

Pneumococcus triggers NFkB degradation in COMMD2 aggresome-like bodies

Abstract

NF-kB driven cellular immunity is essential for both pro- and anti-inflammatory responses to microbes, which makes it one of the most frequently targeted pathways by bacteria during pathogenesis. How NF-kB tunes the epithelial response to Streptococcus pneumoniae across the spectrum of commensal to pathogenic host phenotypic outcomes is not fully understood. In this study, we compare a commensal-like 6B ST90 strain to an invasive TIGR4 isolate and demonstrate that TIGR4 both blunts and antagonizes NF-kB activation. We identified, through comparative mass spectrometry of the p65 interactome, that the 6B ST90 isolate drives a non-canonical NF-kB RelB cascade, whereas TIGR4 induces p65 degradation though aggrephagy. Mechanistically, we show that during TIGR4 challenge a novel interaction of COMMD2 with p65 and p62 is established to mediate degradation of p65. With these results, we establish a role for COMMD2 in negative NF-kB regulation, and present a paradigm for diverging NF-kB responses to pneumococcus. Thus, our studies reveal for the first time a new bacterial pathogenesis mechanism to repress host inflammatory response though COMMD2 mediated turnover of p65.
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pasteur-04097504 , version 1 (15-05-2023)

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Michael G Connor, Lisa Sanchez, Christine Chevalier, Filipe Carvalho, Matthew G Eldridge, et al.. Pneumococcus triggers NFkB degradation in COMMD2 aggresome-like bodies. 2023. ⟨pasteur-04097504⟩
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