title: Anaplasma phagocytophilum infects mast cells via alpha1,3-fucosylated but not sialylated glycans and inhibits IgE-mediated cytokine production and histamine release.
abstract: Mast cells are sentinels for infection. Upon exposure to pathogens, they release their stores of proinflammatory cytokines, chemokines, and histamine. Mast cells are also important for the control of certain tick-borne infections. Anaplasma phagocytophilum is an obligate intracellular tick-transmitted bacterium that infects neutrophils to cause the emerging disease granulocytic anaplasmosis. A. phagocytophilum adhesion to and infection of neutrophils depend on sialylated and α1,3-fucosylated glycans. We investigated the hypotheses that A. phagocytophilum invades mast cells and inhibits mast cell activation. We demonstrate that A. phagocytophilum binds and/or infects murine bone marrow-derived mast cells (BMMCs), murine peritoneal mast cells, and human skin-derived mast cells. A. phagocytophilum infection of BMMCs depends on α1,3-fucosylated, but not sialylated, glycans. A. phagocytophilum binding to and invasion of BMMCs do not elicit proinflammatory cytokine secretion. Moreover, A. phagocytophilum-infected cells are inhibited in the release of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-13, and histamine following stimulation with IgE or antigen. Thus, A. phagocytophilum mitigates mast cell activation. These findings potentially represent a novel means by which A. phagocytophilum usurps host defense mechanisms and shed light on the interplay between mast cells and vector-borne bacterial pathogens.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0678, USA.
authors.forename: Nore
authors.initials: N
authors.lastname: Ojogun
authors.forename: Brian
authors.initials: B
authors.lastname: Barnstein
authors.forename: Bernice
authors.initials: B
authors.lastname: Huang
authors.forename: Carole A
authors.initials: CA
authors.lastname: Oskeritzian
authors.forename: Jonathon W
authors.initials: JW
authors.lastname: Homeister
authors.forename: Daniel
authors.initials: D
authors.lastname: Miller
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Jason A
authors.initials: JA
authors.lastname: Carlyon
mesh_terms: D041081:Anaplasma phagocytophilum / Q000472:pathogenicity* / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D018793:Interleukin-13 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D015850:Interleukin-6; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E