Early Transcriptional Response of Human Neutrophils to<i>Anaplasma phagocytophilum</i>Infection

Sukumaran, Bindu; Carlyon, Jason A.; Cai, Jilian LiJiaxing HuangWanzhi; Berliner, Nancy; Fikrig, Erol

doi:10.1128/iai.73.12.8089-8099.2005

Cited by 44 publications

(45 citation statements)

References 81 publications

(98 reference statements)

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“…In contrast, a different microarray study did not detect an upregulation of cytokines/chemokines in HL-60 cells 3 days after infection with A. phagocytophilum (53) or in NB4 cells 4 h after infection (180). The secretion of IL-8 and CCL20 by neutrophils can be detected 4 and 7 h, respectively, after infection with A. phagocytophilum (6,209). Although the level of IL-8 transcription is relatively low or undetectable in infected neutrophils (32,209), IL-8 protein levels are significantly increased.…”

Section: Generation Of Chemokines/cytokinesmentioning

confidence: 84%

“…The secretion of IL-8 and CCL20 by neutrophils can be detected 4 and 7 h, respectively, after infection with A. phagocytophilum (6,209). Although the level of IL-8 transcription is relatively low or undetectable in infected neutrophils (32,209), IL-8 protein levels are significantly increased. It is important, therefore, to confirm results from mRNA analyses with data on protein levels and function.…”

Section: Generation Of Chemokines/cytokinesmentioning

confidence: 88%

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Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum

2011

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SUMMARY Anaplasma phagocytophilum persists in nature by cycling between mammals and ticks. Human infection by the bite of an infected tick leads to a potentially fatal emerging disease called human granulocytic anaplasmosis. A. phagocytophilum is an obligatory intracellular bacterium that replicates inside mammalian granulocytes and the salivary gland and midgut cells of ticks. A. phagocytophilum evolved the remarkable ability to hijack the regulatory system of host cells. A. phagocytophilum alters vesicular traffic to create an intracellular membrane-bound compartment that allows replication in seclusion from lysosomes. The bacterium downregulates or actively inhibits a number of innate immune responses of mammalian host cells, and it upregulates cellular cholesterol uptake to acquire cholesterol for survival. It also upregulates several genes critical for the infection of ticks, and it prolongs tick survival at freezing temperatures. Several host factors that exacerbate infection have been identified, including interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection include IL-12 and gamma interferon (IFN-γ). Two bacterial type IV secretion effectors and several bacterial proteins that associate with inclusion membranes have been identified. An understanding of the molecular mechanisms underlying A. phagocytophilum infection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease.

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Section: Generation Of Chemokines/cytokinesmentioning

confidence: 84%

Section: Generation Of Chemokines/cytokinesmentioning

confidence: 88%

Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum

2011

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“…This hypothesis is supported by gene expression data predictive of both pro-and antiapoptotic effects. This behavior is not unprecedented as seemingly antagonistic apoptosis-related gene expression has been reported for host cells infected by other intracellular bacteria that exert strong antiapoptotic effects (1,39,55). Among possible proapoptotic signals, expansion of the C. burnetii PV might activate BH3-only proteins (discussed in more detail below).…”

Section: Discussionmentioning

confidence: 98%

Coxiella burnetiiInhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages

2007

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Coxiella burnetii, the cause of human Q fever, is an aerosol-borne, obligate intracellular bacterium that targets host alveolar mononuclear phagocytic cells during infection. In all cell types examined, C. burnetii establishes a replicative niche in a lysosome-like parasitophorous vacuole where it carries out a lengthy infectious cycle with minimal cytopathic effects. The persistent and mild nature of C. burnetii infection in vitro suggests that the pathogen modulates apoptosis to sustain the host cell. In the current study, we examined the ability of C. burnetii to inhibit apoptotic cell death during infection of human THP-1 monocyte-derived macrophages and primary monkey alveolar macrophages. C. burnetii-infected cells demonstrated significant protection from death relative to uninfected cells following treatment with staurosporine, a potent inducer of intrinsic apoptosis. This protection correlated with reduced cleavage of caspase-9, caspase-3, and poly(ADPribose) polymerase (PARP), all proteolytic events that occur during apoptosis. Reduced PARP cleavage was also observed in cells treated with tumor necrosis factor alpha to induce extrinsic apoptosis. Apoptosis inhibition was a C. burnetii-driven process as infected cells treated with rifampin or chloramphenicol, inhibitors of bacterial RNA and protein synthesis, respectively, showed significantly reduced protection against staurosporine-induced apoptosis. C. burnetii infection affected the expression of multiple apoptosis-related genes and resulted in increased synthesis of the antiapoptotic proteins A1/Bfl-1 and c-IAP2. Collectively, these data suggest that C. burnetii modulates apoptotic pathways to inhibit host cell death, thus providing a stable, intracellular niche for the course of the pathogen's infectious cycle.

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“…phagocytophilum undergoes a biphasic developmental cycle, transitioning between an infectious dense-cored (DC) form and a noninfectious, replicative reticulate cell (RC) form. DC bacteria are able to invade and infect promyelocytic and endothelial cell lines (15)(16)(17)(18)(19)(20)(21)(22). Within 4 h of adherence, DC organisms enter host cell-derived vacuoles (23)(24)(25)(26).…”

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confidence: 99%

Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection

et al. 2013

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e Anaplasma phagocytophilum, a member of the family Anaplasmataceae, is the tick-transmitted obligate intracellular bacterium that causes human granulocytic anaplasmosis. The life cycle of A. phagocytophilum is biphasic, transitioning between the noninfectious reticulate cell (RC) and infectious dense-cored (DC) forms. We analyzed the bacterium's DC surface proteome by selective biotinylation of surface proteins, NeutrAvidin affinity purification, and mass spectrometry. Transcriptional profiling of selected outer membrane protein candidates over the course of infection revealed that aph_0248 (designated asp14 [14-kDa A. phagocytophilum surface protein]) expression was upregulated the most during A. phagocytophilum cellular invasion. asp14 transcription was induced during transmission feeding of A. phagocytophilum-infected ticks on mice and was upregulated when the bacterium engaged its receptor, P-selectin glycoprotein ligand 1. Asp14 localized to the A. phagocytophilum surface and was expressed during in vivo infection. Treating DC organisms with Asp14 antiserum or preincubating mammalian host cells with glutathione S-transferase (GST)-Asp14 significantly inhibited infection of host cells. Moreover, preincubating host cells with GST-tagged forms of both Asp14 and outer membrane protein A, another A. phagocytophilum invasin, pronouncedly reduced infection relative to treatment with either protein alone. The Asp14 domain that is sufficient for cellular adherence and invasion lies within the C-terminal 12 to 24 amino acids and is conserved among other Anaplasma and Ehrlichia species. These results identify Asp14 as an A. phagocytophilum surface protein that is critical for infection, delineate its invasion domain, and demonstrate the potential of targeting Asp14 in concert with OmpA for protecting against infection by A. phagocytophilum and other Anaplasmataceae pathogens.

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Early Transcriptional Response of Human Neutrophils toAnaplasma phagocytophilumInfection

Cited by 44 publications

References 81 publications

Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum

Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum

Coxiella burnetiiInhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages

Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection

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