Platelet-activating Factor Receptor Initiates Contact of Acinetobacter baumannii Expressing Phosphorylcholine with Host Cells

Smani, Younes; Docobo-Pérez, Fernando; López-Rojas, Rafael; Domínguez-Herrera, Juan; Ibáñez-Martínez, José; Pachón, Jerónimo

doi:10.1074/jbc.m112.344556

Cited by 61 publications

(76 citation statements)

References 52 publications

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“…baumannii is generally viewed as an extracellular bacterium, but recent reports have shown that A. baumannii can invade lung epithelial cells (14,15) and also get internalized into macrophages (6), indicating that this bacterium also has an intracellular life cycle. The contribution of the intracellular life cycle of A. baumannii in its pathogenesis has yet to be fully defined.…”

Section: Leukin-8 (Il-8) By Lung Epithelial Cells In Vitro During a mentioning

confidence: 99%

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

et al. 2014

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Acinetobacter baumannii is a major extensively drug-resistant lethal human nosocomial bacterium. However, the host innate immune mechanisms controlling A. baumannii are not well understood. Although viewed as an extracellular pathogen, A. baumannii can also invade and survive intracellularly. However, whether host innate immune pathways sensing intracellular bacteria contribute to immunity against A. baumannii is not known. Here, we provide evidence for the first time that intracellular antibacterial innate immune receptors Nod1 and Nod2, and their adaptor Rip2, play critical roles in the sensing and clearance of A. baumannii by human airway epithelial cells in vitro. A. baumannii infection upregulated Rip2 expression. Silencing of Nod1, Nod2, and Rip2 expression profoundly increased intracellular invasion and prolonged the multiplication and survival of A. baumannii in lung epithelial cells. Notably, the Nod1/2-Rip2 axis did not contribute to the control of A. baumannii infection of human macrophages, indicating that they play cell type-specific roles. The Nod1/2-Rip2 axis was needed for A. baumannii infection-induced activation of NF-B but not mitogen-activated protein kinases. Moreover, the Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to A. baumannii infection. Mechanistic studies showed that the Nod1/2 pathway contributed to the innate control of A. baumannii infection through the production of ␤-defensin 2 by airway epithelial cells. This study revealed new insights into the immune control of A. baumannii and may contribute to the development of effective immune therapeutics and vaccines against A. baumannii.

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Section: Leukin-8 (Il-8) By Lung Epithelial Cells In Vitro During a mentioning

confidence: 99%

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

et al. 2014

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“…Bacterial species, including H. influenzae, S. pneumoniae, Aggregatibacter actinomycetemcomitans, H. somni, P. aeruginosa, and commensal Neisseria strains, exhibit this version of molecular mimicry, allowing binding to PAFr in vitro (51)(52)(53)(54). PAFr binding also increases cell invasion for several bacterial species, including S. pneumoniae, P. aeruginosa, A. actinomycetemcomitans, and Acinetobacter baumannii (27,51,52,55). Invasion of epithelial cells allows bacteria to avoid extracellular immune responses, although intracellular survival is dependent on evasion of antibacterial intracellular immunity.…”

Section: Chop Affects Host Recognitionmentioning

confidence: 99%

Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine

Clark

Weiser

2013

Infect Immun

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All microorganisms dependent on persistence in a host for survival rely on either hiding from or modulating host responses to infection. The small molecule phosphorylcholine, or choline phosphate (ChoP), is used for both of these purposes by a wide array of bacterial and parasitic microbes. While the mechanisms underlying ChoP acquisition and expression are diverse, a unifying theme is the use of ChoP to reduce the immune response to infection, creating an advantage for ChoP-expressing microorganisms. In this minireview, we discuss several benefits of ChoP expression during infection as well as how the immune system fights back against ChoP-expressing pathogens.

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“…S. pneumoniae required the scaffold function of the β-arrestins to recruit clathrin in PAFR-mediated endocytosis by endothelial cells (Radin et al, 2005). Besides, Smani et al (2012) reported that clathrin and β-arrestin-1 and 2 are involved in A. baumannii invasion of lung epithelial cells. In this study, we found that clathrin inhibitors MDC and CPZ significantly inhibited A. actinomycetemcomitans bearing PC invasion of HUVEC.…”

Section: Discussionmentioning

confidence: 99%

“…The role of β-arrestins in inflammation process has been well known by regulation of chemokine responsiveness (Vroon et al, 2006;Cattaruzza et al, 2013;Porter et al, 2010). It has been reported that clathrin and β-arrestin-1 could mediate S. pneumonia and Acinetobacter baumannii invasion of epithelial cells (Radin et al, 2005;Smani et al, 2012). However, there are no studies about clathrin and β-arrestins in A. actinomycetemcomitans internalizetion by epithelial or endothelial cells.…”

Section: Primermentioning

confidence: 99%

Involvement of clathrin and -arrestins in Aggregatibacter actinomycetemcomitans endocytosis of human vascular endothelial cells

Wang¹,

Li²,

JingYi³

et al. 2014

Afr. J. Microbiol. Res.

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Phosphorylcholine (PC) has been reported to help PC-bearing Aggregatibacter actinomycetemcomitans to gain access to the general circulation via interaction with the platelet-activating factor receptor (PAFR) on endothelial cells. However, the underlying mechanism remains unclear. Here, we found that inhibition of clathrin and β-arrestins blocked bacterial PC binding to PAFR which significantly attenuated A. actinomycetemcomitans invasion of human vascular endothelial cells (HUVEC). These results demonstrated the involvement of clathrin and β-arrestins in PC-bearing A. actinomycetemcomitans invasion of HUVEC.

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Platelet-activating Factor Receptor Initiates Contact of Acinetobacter baumannii Expressing Phosphorylcholine with Host Cells

Cited by 61 publications

References 52 publications

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

The Nod1, Nod2, and Rip2 Axis Contributes to Host Immune Defense against Intracellular Acinetobacter baumannii Infection

Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine

Involvement of clathrin and -arrestins in Aggregatibacter actinomycetemcomitans endocytosis of human vascular endothelial cells

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