Experimental Legionella longbeachae infection in intratracheally inoculated mice

Gobin, Ivana; Šuša, Milorad; Begić, Gabrijela; Hartland, Elizabeth L.; Dorić, Miljenko

doi:10.1099/jmm.0.007476-0

Cited by 22 publications

(34 citation statements)

References 23 publications

(20 reference statements)

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“…Notably, the closely related, soil-living pathogen Legionella longbeachae lacks genes for flagellum biosynthesis and may thus avoid recognition by mammalian pattern recognition receptors such as NLRC4 (25,51,55). This feature may account for why L. longbeachae is highly and often lethal in mouse models of infection (46,56).…”

Section: Discussionmentioning

confidence: 99%

Activation of NLRC4 by Flagellated Bacteria Triggers Caspase-1–Dependent and –Independent Responses To Restrict Legionella pneumophila Replication in Macrophages and In Vivo

Pereira

Morgantetti

Massis

et al. 2011

The Journal of Immunology

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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, fliI, and flaA, we found that flagellin and motility are important for the colonization of the protozoan host Acanthamoeba castellanii. However, in macrophages and mammalian lungs, flagellin expression abrogated bacterial replication. The flagellin-mediated growth restriction was dependent on NLRC4, and although it was recently demonstrated that NLRC4 is able to recognize bacteria independent of flagellin, we found that the NLRC4-dependent restriction of L. pneumophila multiplication was fully dependent on flagellin. By examining infected caspase-1−/− mice and macrophages with flaA, fliI, and WT L. pneumophila, we could detect greater replication of flaA, which suggests that caspase-1 only partially accounted for flagellin-dependent growth restriction. Conversely, WT L. pneumophila multiplied better in macrophages and mice deficient for NLRC4 compared with that in macrophages and mice deficient for caspase-1, supporting the existence of a novel caspase-1–independent response downstream of NLRC4. This response operated early after macrophage infection and accounted for the restriction of bacterial replication within bacteria-containing vacuoles. Collectively, our data indicate that flagellin is required for NLRC4-dependent responses to L. pneumophila and that NLRC4 triggers caspase-1–dependent and –independent responses for bacterial growth restriction in macrophages and in vivo.

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Section: Discussionmentioning

confidence: 99%

Activation of NLRC4 by Flagellated Bacteria Triggers Caspase-1–Dependent and –Independent Responses To Restrict Legionella pneumophila Replication in Macrophages and In Vivo

Pereira

Morgantetti

Massis

et al. 2011

The Journal of Immunology

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“…While only A/J mice are permissive for replication of L. pneumophila , A/J, C57BL/6, and BALB/c mice are all permissive for replication of L. longbeachae (Asare et al, 2007; Gobin et al, 2009). Resistance of C57BL/6 and BALB/c mice to L. pneumophila has been attributed to polymorphisms in Nod-like receptor apoptosis inhibitory protein 5 ( naip5 ) allele that recognizes the C-terminus of flagellin (Wright et al, 2003; Molofsky et al, 2006; Ren et al, 2006; Lightfield et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Comparative and Functional Genomics of Legionella Identified Eukaryotic Like Proteins as Key Players in Host?Pathogen Interactions

Gómez-Valero¹,

Rusniok²,

Cazalet³

et al. 2011

Front. Microbio.

133

120

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Although best known for its ability to cause severe pneumonia in people whose immune defenses are weakened, Legionella pneumophila and Legionella longbeachae are two species of a large genus of bacteria that are ubiquitous in nature, where they parasitize protozoa. Adaptation to the host environment and exploitation of host cell functions are critical for the success of these intracellular pathogens. The establishment and publication of the complete genome sequences of L. pneumophila and L. longbeachae isolates paved the way for major breakthroughs in understanding the biology of these organisms. In this review we present the knowledge gained from the analyses and comparison of the complete genome sequences of different L. pneumophila and L. longbeachae strains. Emphasis is given on putative virulence and Legionella life cycle related functions, such as the identification of an extended array of eukaryotic like proteins, many of which have been shown to modulate host cell functions to the pathogen’s advantage. Surprisingly, many of the eukaryotic domain proteins identified in L. pneumophila as well as many substrates of the Dot/Icm type IV secretion system essential for intracellular replication are different between these two species, although they cause the same disease. Finally, evolutionary aspects regarding the eukaryotic like proteins in Legionella are discussed.

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“…A study of the ability of L. longbeachae isolates to infect guinea pigs also demonstrated that there was a substantial variation in the virulences of different L. longbeachae strains in this infection model (110). Strains of L. longbeachae serogroup 1 are highly virulent in mice, with the intratracheal inoculation of 10 3 bacteria capable of causing disease (148). Unlike L. pneumophila, mouse infection with L. longbeachae is not restricted to A mice, and both BALB/c and C57BL/6 mice are also susceptible to infection with serogroup 1 strains (148).…”

Section: Responses In Micementioning

confidence: 99%

“…However, even in A mice, the infection is self-limiting. The exception to the general rule of murine resistance to Legionella infection is L. longbeachae, which is highly virulent for a variety of inbred mouse strains (148). Several other Legionella species also replicate in murine macrophages (181,355) and, if given a high-enough inoculum, may also replicate in whole animals.…”

Section: Immune Responses To Legionella Infectionmentioning

confidence: 99%

“…Strains of L. longbeachae serogroup 1 are highly virulent in mice, with the intratracheal inoculation of 10 3 bacteria capable of causing disease (148). Unlike L. pneumophila, mouse infection with L. longbeachae is not restricted to A mice, and both BALB/c and C57BL/6 mice are also susceptible to infection with serogroup 1 strains (148). This difference in virulence may in part be related to the fact that L. longbeachae serogroup 1 strains are nonmotile, as the deletion of flagellin from L. pneumophila also increases the virulence and host range of the pathogen for mice (148,273).…”

Section: Responses In Micementioning

confidence: 99%

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Molecular Pathogenesis of Infections Caused byLegionella pneumophila

Newton¹,

et al. 2010

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SUMMARY The genus Legionella contains more than 50 species, of which at least 24 have been associated with human infection. The best-characterized member of the genus, Legionella pneumophila, is the major causative agent of Legionnaires' disease, a severe form of acute pneumonia. L. pneumophila is an intracellular pathogen, and as part of its pathogenesis, the bacteria avoid phagolysosome fusion and replicate within alveolar macrophages and epithelial cells in a vacuole that exhibits many characteristics of the endoplasmic reticulum (ER). The formation of the unusual L. pneumophila vacuole is a feature of its interaction with the host, yet the mechanisms by which the bacteria avoid classical endosome fusion and recruit markers of the ER are incompletely understood. Here we review the factors that contribute to the ability of L. pneumophila to infect and replicate in human cells and amoebae with an emphasis on proteins that are secreted by the bacteria into the Legionella vacuole and/or the host cell. Many of these factors undermine eukaryotic trafficking and signaling pathways by acting as functional and, in some cases, structural mimics of eukaryotic proteins. We discuss the consequences of this mimicry for the biology of the infected cell and also for immune responses to L. pneumophila infection.

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Experimental Legionella longbeachae infection in intratracheally inoculated mice

Cited by 22 publications

References 23 publications

Activation of NLRC4 by Flagellated Bacteria Triggers Caspase-1–Dependent and –Independent Responses To Restrict Legionella pneumophila Replication in Macrophages and In Vivo

Activation of NLRC4 by Flagellated Bacteria Triggers Caspase-1–Dependent and –Independent Responses To Restrict Legionella pneumophila Replication in Macrophages and In Vivo

Comparative and Functional Genomics of Legionella Identified Eukaryotic Like Proteins as Key Players in Host?Pathogen Interactions

Molecular Pathogenesis of Infections Caused byLegionella pneumophila

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