The human NAIP-NLRC4-inflammasome senses the <i>Pseudomonas aeruginosa</i> T3SS inner-rod protein

Grandjean, Teddy; Boucher, Anne; Thépaut, Marion; Monlezun, Laura; Guery, Benoît; Faudry, Eric; Kipnis, Éric; Dessein, Rodrigue

doi:10.1093/intimm/dxx047

Cited by 44 publications

(38 citation statements)

References 20 publications

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“…Furthermore, a single human NAIP isoform can mediate inflammasome responses to all three bacterial proteins in contrast to mouse NAIPs, which are highly selective for recognition of individual flagellin or T3SS proteins (6)(7)(8)(9)(10)(11). Consistent with our findings, a recent study found that the Pseudomonas aeruginosa T3SS inner rod also activates the human NAIP inflammasome (46). The region of murine NAIPs that confers ligand specificity has been mapped to an internal region composed of several nucleotide-binding domain (NBD)associated α-helical domains (45).…”

Section: Discussionsupporting

confidence: 91%

Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome

Ruiz

Ramirez

Naseer

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

157

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Inflammasomes are cytosolic multiprotein complexes that initiate host defense against bacterial pathogens by activating caspase-1-dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) activate the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4) inflammasome upon sensing components of the type III secretion system (T3SS) and flagellar apparatus. NAIP1 recognizes the T3SS needle protein, NAIP2 recognizes the T3SS inner rod protein, and NAIP5 and NAIP6 recognize flagellin. In contrast, humans encode a single functional NAIP, raising the question of whether human NAIP senses one or multiple bacterial ligands. Previous studies found that human NAIP detects both flagellin and the T3SS needle protein and suggested that the ability to detect both ligands was achieved by multiple isoforms encoded by the single human gene. Here, we show that human NAIP also senses the Typhimurium T3SS inner rod protein PrgJ and that T3SS inner rod proteins from multiple bacterial species are also detected. Furthermore, we show that a single human NAIP isoform is capable of sensing the T3SS inner rod, needle, and flagellin. Our findings indicate that, in contrast to murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred by a single human NAIP.

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Section: Discussionsupporting

confidence: 91%

Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome

Ruiz

Ramirez

Naseer

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

157

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“…Bacterial flagellin and evolutionarily conserved rod and needle proteins of the type 3 secretion system (T3SS) injectisome of some Gram‐negative bacteria are recognised by the NAIPs, leading to the assembly of the NLRC4 inflammasome in macrophages (Miao, Mao, et al, ; Zhao et al, ). There are seven mouse Naip genes, four of which recognise different ligands (Kofoed & Vance, 2011; Zhao et al, ), while humans only encode one NAIP gene that can recognise a similar repertoire of ligands (Yang, Zhao, Shi, & Shao, ; Kortmann, Brubaker, & Monack, ; Grandjean et al, ; Reyes Ruiz et al, ).…”

Section: Signals For Inflammasome Activationmentioning

confidence: 99%

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Sanchez‐Garrido

Slater

Clements

et al. 2020

Cellular Microbiology

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Enteric pathogen–host interactions occur at multiple interfaces, including the intestinal epithelium and deeper organs of the immune system. Microbial ligands and activities are detected by host sensors that elicit a range of immune responses. Membrane‐bound toll‐like receptors and cytosolic inflammasome pathways are key signal transducers that trigger the production of pro‐inflammatory molecules, such as cytokines and chemokines, and regulate cell death in response to infection. In recent years, the inflammasomes have emerged as a key frontier in the tussle between bacterial pathogens and the host. Inflammasomes are complexes that activate caspase‐1 and are regulated by related caspases, such as caspase‐11, ‐4, ‐5 and ‐8. Importantly, enteric bacterial pathogens can actively engage or evade inflammasome signalling systems. Extracellular, vacuolar and cytosolic bacteria have developed divergent strategies to subvert inflammasomes. While some pathogens take advantage of inflammasome activation (e.g. Listeria monocytogenes, Helicobacter pylori), others (e.g. E. coli, Salmonella, Shigella, Yersinia sp.) deploy a range of virulence factors, mainly type 3 secretion system effectors, that subvert or inhibit inflammasomes. In this review we focus on inflammasome pathways and their immune functions, and discuss how enteric bacterial pathogens interact with them. These studies have not only shed light on inflammasome‐mediated immunity, but also the exciting area of mammalian cytosolic immune surveillance.

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“…Exoenzyme S (ExoS) shows ADP-ribosyltransferase (ADPRT) activity, and it is a major characteristic of patients with acute lung injuries who are also infected with P. aeruginosa among these secretory toxins [7,8]. Injected ExoS is known to convert pro-interleukin (IL-1β) into IL-1β via NLRC4 or NLRP3 and caspase-1 in infected mammalian cells by P. aeruginosa [9,10]. In addition, it produces other pro-in ammatory cytokines IL-18, IL-6, and tumor necrosis factor α (TNF-α) through the nuclear factor κB (NF-κB) pathway [11].…”

mentioning

confidence: 99%

Quercetin attenuates the production of pro-inflammatory cytokines in H292 human lung epithelial cells infected with Pseudomonas aeruginosa, by modulating ExoS production

Ahn

Park

Jang

et al. 2020

Preprint

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Background: The type three secretion system (T3SS) is a major virulence system of Pseudomonas aeruginosa (P. aeruginosa). The effector protein Exotoxin S (ExoS) produced by P. aeruginosa is secreted into the host cells via the T3SS. For the purpose of screening the inhibitors with regard to ExoS secretion, we developed the sandwich-type enzyme-linked immunosorbent assay (ELISA) system. From the initial screening, quercetin was selected because it has the prominent effect of ExoS inhibition and also is known to have anti-inflammatory and antioxidant effects on mammalian cells.Results: In this study, we investigated the effects of quercetin on the expression and secretion of ExoS using the ELISA and Western blot analysis methods. The results showed that the secretion of ExoS was significantly decreased by 10, 20uM quercetin. Also, pscF and popD, which are composed of the T3SS needle, are reduced by quercetin at the mRNA level, and we confirmed the inhibitory effect of quercetin on cytokines in P. aeruginosa-infected H292 cells by real-time polymerase chain reaction (PCR). Conclusion: Collectively, quercetin inhibits the secretion of ExoS by reducing both ExoS production and the expression of the needle protein of T3SS. Furthermore, these results suggest that quercetin has the potential to be used as an anti-toxic treatment for the disease caused by P. aeruginosa infection.

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The human NAIP-NLRC4-inflammasome senses the Pseudomonas aeruginosa T3SS inner-rod protein

Cited by 44 publications

References 20 publications

Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome

Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Quercetin attenuates the production of pro-inflammatory cytokines in H292 human lung epithelial cells infected with Pseudomonas aeruginosa, by modulating ExoS production

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