Inflammasome Activation by Campylobacter jejuni

Abstract

The Gram-negative pathogen Campylobacter jejuni is the most common cause of bacterial foodborne disease worldwide. The mechanisms that lead to bacterial invasion of eukaryotic cells and massive intestinal inflammation are still unknown. In this study, we report that C. jejuni infection of mouse macrophages induces upregulation of pro–IL-1β transcript and secretion of IL-1β without eliciting cell death. Immunoblotting indicated cleavage of caspase-1 and IL-1β in infected cells. In bone marrow–derived macrophages from different knockout mice, IL-1β secretion was found to require NLRP3, ASC, and caspase-1/11 but not NLRC4. In contrast to NLRP3 activation by ATP, C. jejuni activation did not require priming of these macrophages. C. jejuni also activated the NLRP3 inflammasome in human macrophages as indicated by the presence of ASC foci and caspase-1–positive cells. Analysis of a vast array of C. jejuni mutants with defects in capsule formation, LPS biosynthesis, chemotaxis, flagella synthesis and flagellin (-like) secretion, type 6 secretion system needle protein, or cytolethal distending toxin revealed a direct correlation between the number of intracellular bacteria and NLRP3 inflammasome activation. The C. jejuni invasion–related activation of the NLRP3 inflammasome without cytotoxicity and even in nonprimed cells extends the known repertoire of bacterial inflammasome activation and likely contributes to C. jejuni–induced intestinal inflammation.

Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus

“…Given that C. concisus UNSWCD does not have a classical type III secretion system (its flagellum acts as a type III export system) or a type IV secretion system (21), it is possible that NLRC4 is not a major sensor of C. concisus infection. Our results for NLRP3 and NLRC4 are in line with the recent findings of Bouwman and colleagues showing that IL-1B secretion following C. jejuni infection was dependent on invasion-related activation of the NLRP3 inflammasome and not NLRC4 (35). Of the other genes encoding CARD-containing members within the NLR family, NLRC5, encoding a potential regulator of interferon signaling and production of major histocompatibility complex (MHC) class I molecules (36)(37)(38), was upregulated upon infection with C. concisus (Tables 1 and 2).…”

Baicalin suppresses NLRP3 inflammasome and nuclear factor-kappa B (NF-κB) signaling during Haemophilus parasuis infection

“…In addition, some bacteria have been implicated in activation of the NLRP3 inflammasome [ 54 , 55 ]. For example, Campylobacter jejuni could activate NLRP3 inflammasome and induce IL-1β secretion in mouse macrophages without eliciting cell death [ 56 ]. Our lab has previously demonstrated that the expression of NLRP3 is stimulated in piglet mononuclear phagocytes induced by LPS and baicalin could inhibit the NLRP3 inflammasome expression [ 19 ].…”

NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection

“…cDNA synthesis was carried out by iScript cDNA Synthesis Kit (170-8891; Bio-Rad, Hercules, CA) as per the manufacturer's instructions. Primer sequences for various genes amplified were as described in Bouwman et al 56 Reactions were performed in Roche Light Cycler 480 Real-time PCR system under the following conditions: 94 1C/2 min for 1 cycle; 94 1C/30 s, 50 1C/30 s, 72 1C/60 s for 40 cycles; 72 1C/7 min for 1 cycle.…”