1. The human NAIP-NLRC4-inflammasome senses the Pseudomonas aeruginosa T3SS inner-rod protein
- Author
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Marion Thepaut, Laura Monlezun, B. Guery, Eric Faudry, Eric Kipnis, Rodrigue Dessein, Teddy Grandjean, Anne Boucher, Université de Lille, Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)
- Subjects
0301 basic medicine ,Inflammasomes ,THP-1 Cells ,Interleukin-1beta ,medicine.disease_cause ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Type three secretion system ,Mice ,0302 clinical medicine ,NLRC4 ,Type III Secretion Systems ,Immunology and Allergy ,Toll-like receptor ,biology ,Chemistry ,Caspase 1 ,NOD-like receptor ,Inflammasome ,General Medicine ,Neuronal Apoptosis-Inhibitory Protein ,Innate Immunity ,Salmonella enterica ,Pseudomonas aeruginosa ,Intercellular Signaling Peptides and Proteins ,medicine.drug ,Immunology ,Microbiology ,03 medical and health sciences ,Pathogen-associated microbial pattern ,medicine ,Animals ,Humans ,Pseudomonas Infections ,Nod-like receptor ,Macrophages ,Calcium-Binding Proteins ,Pathogen-Associated Molecular Pattern Molecules ,biology.organism_classification ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Immunity, Innate ,Toll-Like Receptor 2 ,CARD Signaling Adaptor Proteins ,Toll-Like Receptor 4 ,030104 developmental biology ,bacteria ,NAIP ,Carrier Proteins ,030215 immunology - Abstract
While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1β maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components.
- Published
- 2017
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