Breaking in and grabbing a meal: Anaplasma phagocytophilum cellular invasion, nutrient acquisition, and promising tools for their study

Truchan, Hilary K.; Seidman, David; Carlyon, Jason A.

doi:10.1016/j.micinf.2013.10.010

Cited by 35 publications

(49 citation statements)

References 71 publications

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“…These gene conversion events are critical for generating antigenic diversity and immune evasion that promotes survival and persistence in naturally-infected mammalian hosts [42,43]. A. phagocytophilum also encodes several proteins that are secreted to interact with the pathogen-containing vacuolar membrane that direct vacuolar fusion events by recruiting membrane trafficking proteins [44–49], or several nucleomodulins that translocate into the nucleus, including AnkA which exerts transcriptional regulating effects on genes critical for host microbicidal activity by altering chromatin structure and perhaps DNA methylation [50–56]. Other changes in host transcription with infection include a marked upregulation in chemokine and proinflammatory cytokine expression [57,58].…”

Section: Anaplasmataceaementioning

confidence: 99%

The role of CD8 T lymphocytes in rickettsial infections

Walker

Dumler

2015

Semin Immunopathol

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Arthropod-borne obligately intracellular bacteria pose a difficult challenge to the immune system. The genera Rickettsia, Orientia, Ehrlichia, and Anaplasma evolved mechanisms of immune evasion, and each interacts differently with the immune system. The roles of CD8 T cells include protective immunity and immunopathology. In Rickettsia infections, CD8 T cells are protective mediated in part by cytotoxicity toward infected cells. In contrast, TNFα overproduction by CD8 T cells is pathogenic in lethal ehrlichiosis by induction of apoptosis/necrosis in hepatocytes. Yet, CD8 T cells, along with CD4 T cells and antibodies, also contribute to protective immunity in ehrlichial infections. In granulocytic anaplasmosis, CD8 T cells impact pathogen control modestly but could contribute to immunopathology by virtue of their dysfunction. While preliminary evidence indicates that CD8 T cells are important in protection against Orientia tsutsugamushi, mechanistic studies have been neglected. Valid animal models will enable experiments to elucidate protective and pathologic immune mechanisms. The public health need for vaccines against these agents of human disease, most clearly O. tsutsugamushi, and the veterinary diseases, canine monocytotropic ehrlichiosis (E. canis), heartwater (E. ruminantium) and bovine anaplasmosis (A. marginale) requires detailed immunity and immunopathology investigations, including the roles of CD8 T lymphocytes.

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Section: Anaplasmataceaementioning

confidence: 99%

The role of CD8 T lymphocytes in rickettsial infections

Walker

Dumler

2015

Semin Immunopathol

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“…A. phagocytophilum infection in humans, termed human granulocytic anaplasmosis (HGA), is an emerging zoonosis in the USA, Europe and Asia (reviewed by Truchan et al ., 2013). HGA presents as an acute febrile illness characterized by chills, headache, malaise, leucopenia, thrombocytopenia and elevated hepatic aminotransferases.…”

Section: Introductionmentioning

confidence: 99%

Anaplasma phagocytophilumRab10-dependent parasitism of thetrans-Golgi network is critical for completion of the infection cycle

Truchan

VieBrock

Cockburn

et al. 2015

Cellular Microbiology

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Summary Anaplasma phagocytophilum is an emerging human pathogen and obligate intracellular bacterium. It inhabits a host cell-derived vacuole and cycles between replicative reticulate cell (RC) and infectious dense-cored (DC) morphotypes. Host–pathogen interactions that are critical for RC-to-DC conversion are undefined. We previously reported that A. phagocytophilum recruits green fluorescent protein (GFP)-tagged Rab10, a GTPase that directs exocytic traffic from the sphingolipid-rich trans-Golgi network (TGN) to its vacuole in a guanine nucleotide-independent manner. Here, we demonstrate that endogenous Rab10-positive TGN vesicles are not only routed to but also delivered into the A. phagocytophilum-occupied vacuole (ApV). Consistent with this finding, A. phagocytophilum incorporates sphingolipids while intracellular and retains them when naturally released from host cells. TGN vesicle delivery into the ApV is Rab10 dependent, up-regulates expression of the DC-specific marker, APH1235, and is critical for the production of infectious progeny. The A. phagocytophilum surface protein, uridine monophosphate kinase, was identified as a guanine nucleotide-independent, Rab10-specific ligand. These data delineate why Rab10 is important for the A. phagocytophilum infection cycle and expand the understanding of the benefits that exploiting host cell membrane traffic affords intracellular bacterial pathogens.

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“…Previously, we demonstrated that caspase-1-deficient mice were more susceptible than wild-type animals to Anaplasma phagocytophilum infection (8). A. phagocytophilum causes human granulocytic anaplasmosis and colonizes neutrophils during infection (9)(10)(11)(12). However, macrophages are responsible for disease pathology.…”

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confidence: 99%

The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

et al. 2014

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i Saliva from arthropod vectors facilitates blood feeding by altering host inflammation. Whether arthropod saliva counters inflammasome signaling, a protein scaffold that regulates the activity of caspase-1 and cleavage of interleukin-1␤ (IL-1␤) and IL-18 into mature molecules, remains elusive. In this study, we provide evidence that a tick salivary protein, sialostatin L2, inhibits inflammasome formation during pathogen infection. We show that sialostatin L2 targets caspase-1 activity during host stimulation with the rickettsial agent Anaplasma phagocytophilum. A. phagocytophilum causes macrophage activation and hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear factor B or cathepsin L signaling. Reactive oxygen species from NADPH oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory process. Altogether, our data expand the knowledge of immunoregulatory pathways of tick salivary proteins and unveil an important finding in inflammasome biology.

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Breaking in and grabbing a meal: Anaplasma phagocytophilum cellular invasion, nutrient acquisition, and promising tools for their study

Cited by 35 publications

References 71 publications

The role of CD8 T lymphocytes in rickettsial infections

The role of CD8 T lymphocytes in rickettsial infections

Anaplasma phagocytophilumRab10-dependent parasitism of thetrans-Golgi network is critical for completion of the infection cycle

The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

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