Intestinal epithelial NAIP/NLRC4 restricts systemic dissemination of the adapted pathogen Salmonella Typhimurium due to site-specific bacterial PAMP expression
Abstract
Inflammasomes can prevent systemic dissemination of enteropathogenic bacteria. As adapted pathogens including Salmonella Typhimurium (S. Tm) have evolved evasion strategies, it has remained unclear when and where inflammasomes restrict their dissemination. Bacterial population dynamics establish that the NAIP/NLRC4 inflammasome specifically restricts S. Tm migration from the gut to draining lymph nodes. This is solely attributable to NAIP/NLRC4 within intestinal epithelial cells (IECs), while S. Tm evades restriction by phagocyte NAIP/NLRC4. NLRP3 and Caspase-11 also fail to restrict S. Tm mucosa traversal, migration to lymph nodes, and systemic pathogen growth. The ability of IECs (not phagocytes) to mount a NAIP/NLRC4 defense in vivo is explained by particularly high NAIP/NLRC4 expression in IECs and the necessity for epithelium-invading S. Tm to express the NAIP1-6 ligands—flagella and type-III-secretion-system-1. Imaging reveals both ligands to be promptly downregulated following IEC-traversal. These results highlight the importance of intestinal epithelial NAIP/NLRC4 in blocking bacterial dissemination in vivo, and explain why this constitutes a uniquely evasion-proof defense against the adapted enteropathogen S. Tm. Mehr anzeigen
Persistenter Link
https://doi.org/10.3929/ethz-b-000394274Publikationsstatus
publishedExterne Links
Zeitschrift / Serie
Mucosal ImmunologyBand
Seiten / Artikelnummer
Verlag
NatureOrganisationseinheit
03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
09640 - Wetter Slack, Emma / Wetter Slack, Emma
09463 - Pilhofer, Martin / Pilhofer, Martin
03584 - Bonhoeffer, Sebastian / Bonhoeffer, Sebastian
Förderung
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