2011
DOI: 10.4049/jimmunol.1003784
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Activation of NLRC4 by Flagellated Bacteria Triggers Caspase-1–Dependent and –Independent Responses To Restrict Legionella pneumophila Replication in Macrophages and In Vivo

Abstract: Although NLRC4/IPAF activation by flagellin has been extensively investigated, the downstream signaling pathways and the mechanisms responsible for infection clearance remain unclear. In this study, we used mice deficient for the inflammasome components in addition to wild-type (WT) Legionella pneumophila or bacteria deficient for flagellin (flaA) or motility (fliI) to assess the pathways responsible for NLRC4-dependent growth restriction in vivo and ex vivo. By comparing infections with WT L. pneumophila, fli… Show more

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Cited by 85 publications
(88 citation statements)
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“…Our data support the hypothesis that this pathway does not play a role in the restriction of L. pneumophila and L. gratiana infection in vivo (Figs. 4C, 6D, and 7B); this result is supported by previous observations that NLRP3 and ASC are dispensable for the restriction of L. pneumophila replication in vivo (18,19,35). Notably, caspase-11 facilitated the recruitment of neutrophils to the sites of infection via the induction of IL-1a (40).…”
Section: Discussionsupporting
confidence: 76%
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“…Our data support the hypothesis that this pathway does not play a role in the restriction of L. pneumophila and L. gratiana infection in vivo (Figs. 4C, 6D, and 7B); this result is supported by previous observations that NLRP3 and ASC are dispensable for the restriction of L. pneumophila replication in vivo (18,19,35). Notably, caspase-11 facilitated the recruitment of neutrophils to the sites of infection via the induction of IL-1a (40).…”
Section: Discussionsupporting
confidence: 76%
“…The mechanisms underlying NLRC4-mediated host resistance to L. pneumophila infection are still unclear, but pyroptosis has been proposed to be directly involved in host resistance (22). Furthermore, the NLRC4 inflammasome was reported to trigger the restriction of bacterial replication by additional processes dependent on flagellin but independent of caspase-1 and caspase-11 (18). Another pathway for caspase-1 activation has been reported in addition to the flagellin-mediated activation of the NLRC4 inflammasome.…”
mentioning
confidence: 99%
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“…The transition from a replicative phase to a transmissive phase prior to egress coincides with the activation of several virulence traits, including motility and the production of flagellin (17). Cytosolic flagellin induces a proinflammatory response that leads to host cell death through the activation of Naip/Nlrc1 and caspase-1-mediated pyroptosis (59)(60)(61)(62). L. pneumophila may exploit this pathway for egress, whereby activation of the flagellar regulon at late stages of infection triggers host cell lysis and the release of bacteria.…”
Section: Discussionmentioning
confidence: 99%
“…pneumophila flagellin plays a crucial role in the immune response and growth restriction of L. pneumophila in mice (12,29,31). In murine macrophages, flagellin acts as an important PAMP that triggers inflammasome activation and immune signaling (11,12).…”
Section: Discussionmentioning
confidence: 99%