The Legionella pneumophila replication vacuole: making a cosy niche inside host cells

Isberg, Ralph R.; O’Connor, Tamara J.; Heidtman, Matthew

doi:10.1038/nrmicro1967

Cited by 621 publications

(666 citation statements)

References 126 publications

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“…typhimurium, the causative agent of a severe human pneumonia, L. pneumophila also establishes a special vacuole named the Legionella-containing vacuole (LCV) after intruding into host cells. 122 L. pneumophila secrets various E3 ligase-mimic effectors via the Dot/Icm T4SS to maintain its intracellular survival. 123 T4SS, despite sharing structural similarity with T3SS, is extensively distributed in both Gramnegative and -positive bacteria and uniquely manages the translocation of not only effector proteins but also toxins and plasmids into host cells.…”

Section: Shigella Flexnerimentioning

confidence: 99%

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

Chai

Liu

2016

Cell Mol Immunol

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The ubiquitin system comprises enzymes that are responsible for ubiquitination and deubiquitination, as well as ubiquitin receptors that are capable of recognizing and deciphering the ubiquitin code, which act in coordination to regulate almost all host cellular processes, including host-pathogen interactions. In response to pathogen infection, the host innate immune system launches an array of distinct antimicrobial activities encompassing inflammatory signaling, phagosomal maturation, autophagy and apoptosis, all of which are fine-tuned by the ubiquitin system to eradicate the invading pathogens and to reduce concomitant host damage. By contrast, pathogens have evolved a cohort of exquisite strategies to evade host innate immunity by usurping the ubiquitin system for their own benefits. Here, we present recent advances regarding the ubiquitin system-mediated modulation of host-pathogen interplay, with a specific focus on host innate immune defenses and bacterial pathogen immune evasion.

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Section: Shigella Flexnerimentioning

confidence: 99%

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

Chai

Liu

2016

Cell Mol Immunol

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“…In macrophages, L. pneumophila is located within vacuoles, the biogenesis of which resembles autophagy [24,25]. Because SQSTM1 interacts with LC3/Atg8, an essential factor for autophagosome formation [26], we assessed the role of SQSTM1 in autophagy of infected macrophages.…”

Section: Acute Pulmonary Inflammation Is Enhanced In Sqstm1 −/− Micementioning

confidence: 99%

“…3F). These results suggest that SQSTM1 is a negative regulator of acute pulmonary inflammation, possibly by regulating inflammasome activity.In macrophages, L. pneumophila is located within vacuoles, the biogenesis of which resembles autophagy [24,25]. Because SQSTM1 interacts with LC3/Atg8, an essential factor for autophagosome formation [26], we assessed the role of SQSTM1 in autophagy of infected macrophages.…”

mentioning

confidence: 99%

SQSTM1/p62/A170 regulates the severity of Legionella pneumophila pneumonia by modulating inflammasome activity

et al. 2014

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Sequestosome1/A170/p62 (SQSTM1) is a scaffold multifunctional protein involved in several cellular events, such as signal transduction, cell survival, cell death, and inflammation. SQSTM1 expression by macrophages is induced in response to environmental stresses; however, its role in macrophage-mediated host responses to environmental stimuli, such as infectious pathogens, remains unclear. In this study, we investigated the role of SQSTM1 in host responses to Legionella pneumophila, an intracellular pathogen that infects macrophages, in both an SQSTM1-deficient (SQSTM1 −/− ) mouse model and macrophages from these mice. Compared with wild-type (WT) macrophages, the production and secretion of the proinflammatory cytokine IL-1β was significantly enhanced in SQSTM1 −/− macrophages after infection with L. pneumophila. Inflammasome activity, indicated by the level of IL-18 and caspase-1 activity, was also elevated in SQSTM1 −/− macrophages after infection with L. pneumophila. SQSTM1 may interact with nucleotide-binding oligomerization domain-like receptor family, caspase recruitment domain-containing 4 and nucleotide-binding oligomerization domain like receptor family, pyrin domain containing 3 proteins to inhibit their self-dimerization. Acute pulmonary inflammation induced by L. pneumophila and silica was enhanced in SQSTM1 −/− mice with an increase in IL-1β levels in the bronchoalveolar lavage fluids. These findings suggest that SQSTM1 is a negative regulator of acute pulmonary inflammation, possibly by regulating inflammasome activity and subsequent proinflammatory cytokine production. Keywords:Inflammasome r Legionella r Macrophages r Pneumonia r Sequestosome1Additional supporting information may be found in the online version of this article at the publisher's web-site Sequestosome1/A170/p62 (SQSTM1) is an intracellular protein initially identified as a phosphotyrosine-independent ligand of the Src homology 2 domain of p56lck [6]. Mouse A170, homologous to human SQSTM1, was first identified in macrophages as a stress-inducible intracellular protein [7]. Currently, SQSTM1 is thought to be a multifunctional protein that forms part of a hub for various signal transduction pathways involved in cell survival, cell death, and response to environmental stimuli, through associating with a large number of proteins [8].Studies using genetically modified mice have shown that SQSTM1 plays critical roles in the pathogenesis of numerous diseases, including bone remodeling, obesity, and cancer [9][10][11]. However, the contribution of SQSTM1 to host responses against infectious pathogens remains unclear. In this study, we investigated the role of SQSTM1 in the host responses to L. pneumophila using a SQSTM1-deficient (SQSTM1 −/− ) mouse model and SQSTM1 −/− macrophages. Results and discussion IL-1β secretion is enhanced in SQSTM1 −/− macrophages after Legionella infectionBecause macrophages are the main target cells for L. pneumophila, we first examined the responses to L. pneumophila in macrophages obtained from WT and SQSTM...

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“…Within both evolutionarily distant host cells, L. pneumophila evades endocytic fusion and intercepts ER to Golgi vesicle traffic to remodel its phagosome into an ER-derived vacuole (Kagan and Roy, 2002;Molmeret et al, 2005;Shin and Roy, 2008;Isberg et al, 2009). The Dot/Icm type IV secretion system (Segal et al, 1998;Vogel et al, 1998) injects into the host cell a cadre of 200 effectors to modulate a myriad of cellular processes to reprogram the host cell into a proliferation niche (de Felipe et al, 2008;Shin and Roy, 2008;Isberg et al, 2009). The Ankyrin B (AnkB) effector is injected into the host cell by the Dot/Icm system upon bacterial attachment to the plasma membrane and exploits an evolutionarily conserved eukaryotic machinery within mammalian and protozoan cells (Price et al, 2009).…”

mentioning

confidence: 99%

“…The Legionnaires' disease-causing bacterium, Legionella pneumophila, replicates within alveolar macrophages, causing pneumonia (Isberg et al, 2009). The organism is transmitted to humans from the aquatic environment where L. pneumophila replicates within amoeba and ciliates (Molmeret et al, 2005;Franco et al, 2009).…”

mentioning

confidence: 99%

Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector ofLegionella pneumophila

Price¹,

Al-Quadan²,

Šantić³

et al. 2010

J Cell Biol

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The Legionella pneumophila replication vacuole: making a cosy niche inside host cells

Cited by 621 publications

References 126 publications

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

SQSTM1/p62/A170 regulates the severity of Legionella pneumophila pneumonia by modulating inflammasome activity

Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector ofLegionella pneumophila

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