Mucosal immunology, 2020-05, Vol.13 (3), p.530-544
2020
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Details
- Autor(en) / Beteiligte
- Titel
- Intestinal epithelial NAIP/NLRC4 restricts systemic dissemination of the adapted pathogen Salmonella Typhimurium due to site-specific bacterial PAMP expression
- Ist Teil von
- Mucosal immunology, 2020-05, Vol.13 (3), p.530-544
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1933-0219, 1935-3456eISSN: 1935-3456DOI: 10.1038/s41385-019-0247-0Titel-ID: cdi_swepub_primary_oai_DiVA_org_uu_425657
- Format
- –
- Schlagworte
- Animals, Bacteria, Calcium-Binding Proteins - metabolism, CARD Signaling Adaptor Proteins - metabolism, Caspase-11, Caspases - metabolism, Disease Models, Animal, Epithelial cells, Epithelium, Flagella, Host-Pathogen Interactions - genetics, Host-Pathogen Interactions - immunology, Humans, Inflammasomes, Intestinal Mucosa - immunology, Intestinal Mucosa - metabolism, Intestinal Mucosa - microbiology, Intestine, Ligands, Lymph nodes, Lymphatic system, Lymphoid Tissue - immunology, Lymphoid Tissue - metabolism, Mice, Mice, Knockout, Mucosa, Neuronal Apoptosis-Inhibitory Protein - metabolism, NLR Family, Pyrin Domain-Containing 3 Protein - metabolism, Organ Specificity - immunology, Pathogen-Associated Molecular Pattern Molecules, Pathogens, Phagocytes, Phagocytes - immunology, Phagocytes - metabolism, Population dynamics, Salmonella, Salmonella Infections - immunology, Salmonella Infections - metabolism, Salmonella Infections - microbiology, Salmonella Typhimurium, Salmonella typhimurium - genetics, Salmonella typhimurium - immunology