2006
DOI: 10.1083/jcb1732oia4
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Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection

Abstract: Macrophages are the guardians of the innate immune system, recognizing a broad array of pathogen-associated molecular patterns (PAMPs) to initiate immediate defenses and to recruit the adaptive branch of the immune system. Toll-like receptors (TLRs) detect extracellular microbial products, such as lipopolysaccharide, peptidoglycan, lipotechoic acid, and fl agellin (1), whereas surveillance of the cytosol is the task of nucleotide-binding oligomerization domain (NOD) leucine-rich repeat (LRR) proteins. The best… Show more

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Cited by 99 publications
(187 citation statements)
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References 46 publications
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“…Furthermore, flagellin is responsible for growth restriction of L. pneumophila in mouse macrophages, as cytosolic flagellin is recognized by the macrophages that responds by a Naip5 and a caspase 1-dependent mechanism to restrict bacterial replication and release proinflammatory cytokines. In agreement, flagellindeficient Legionella mutants are able to evade caspase-1-and Naip5-mediated macrophage immunity [53,54]. Moreover, other virulence-associated traits might be regulated by the different regulators involved in the flagella regulatory cascade, given that mutants not expressing flagella have lower virulence [50,52,55].…”
Section: Introductionmentioning
confidence: 86%
“…Furthermore, flagellin is responsible for growth restriction of L. pneumophila in mouse macrophages, as cytosolic flagellin is recognized by the macrophages that responds by a Naip5 and a caspase 1-dependent mechanism to restrict bacterial replication and release proinflammatory cytokines. In agreement, flagellindeficient Legionella mutants are able to evade caspase-1-and Naip5-mediated macrophage immunity [53,54]. Moreover, other virulence-associated traits might be regulated by the different regulators involved in the flagella regulatory cascade, given that mutants not expressing flagella have lower virulence [50,52,55].…”
Section: Introductionmentioning
confidence: 86%
“…Legionella modulates the expression of host cell apoptotic and anti-apoptotic genes to prevent the premature termination of its intracellular replication. In particular, the presence of flagellin and a competent Dot/Icm secretion system are critical for Legionella to regulate the apoptotic process (Amer et al, 2006;Molofsky et al, 2006;Abu-Zant et al, 2007;Santic et al, 2007;Shin and Roy, 2008). In this context, the loss of virulence of Virstrain should give an explanation on how severely damaged the type IV secretion system was, and the absence of flagellin signal could determine the de-regulation of the apoptotic process.…”
Section: (C)mentioning
confidence: 97%
“…Naip5 belongs to the NACHT-LRR (NLR) protein family, a group of cytoplasmic proteins involved in intracellular recognition of conserved structures shared by many pathogens, called pathogen-associated molecular patterns (PAMPs). It has been shown that Naip5 can activate caspase 1 following phagocytosis of L. pneumophila by macrophages (Molofsky et al, 2006;Ren et al, 2006). This process obviously antagonizes the ability of L. pneumophila to remodel its phagosome.…”
Section: Transcriptional Changes and Regulation During The Biphasic Lmentioning
confidence: 99%