title: Murine neutrophils require alpha1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum.
abstract: Anaplasma phagocytophilum causes human granulocytic ehrlichiosis, the second most common tick-borne disease in the United States. Mice are natural reservoirs for this bacterium and man is an inadvertent host. A phagocytophilum's tropism for human neutrophils is linked to neutrophil expression of P-selectin glycoprotein ligand-1 (PSGL-1), as well as sialylated and alpha1,3-fucosylated glycans. To determine whether A phagocytophilum uses similar molecular features to infect murine neutrophils, we assessed in vitro bacterial binding to neutrophils from and infection burden in wild-type mice; mice lacking alpha 1,3-fucosyltransferases Fuc-TIV and Fuc-TVII; or mice lacking PSGL-1. Binding to Fuc-TIV-/-/Fuc-TVII-/- neutrophils and infection of Fuc-TIV-/-/Fuc-TVII-/- mice were significantly reduced relative to wild-type mice. A phagocytophilum binding to PSGL-1-/- neutrophils was modestly reduced, whereas sialidase treatment significantly decreased binding to both wild-type and PSGL-1-/- neutrophils. A phagocytophilum similarly infected PSGL-1-/- and wild-type mice in vivo. A phagocytophilum induced comparable levels of chemokines from wild-type and PSGL-1-/- neutrophils in vitro, while those induced from Fuc-TIV-/-/Fuc-TVII-/- neutrophils were appreciably reduced. Therefore, A phagocytophilum infection in mice, as in humans, requires sialylation and alpha1,3-fucosylation of neutrophils. However, murine infection does not require neutrophil PSGL-1 expression, which has important implications for understanding how A phagocytophilum binds and infects neutrophils.
authors.affiliation: Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Carlyon
authors.forename: Mustafa
authors.initials: M
authors.lastname: Akkoyunlu
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Yago
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.forename: Rodger P
authors.initials: RP
authors.lastname: McEver
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D041081:Anaplasma phagocytophilum / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion; D018925:Chemokines / Q000096:biosynthesis; D016873:Ehrlichiosis / Q000209:etiology / Q000473:pathology; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009439:Neuraminidase; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology*; D011134:Polysaccharides; D011485:Protein Binding
chemical_list: D018925:Chemokines; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011134:Polysaccharides; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D009439:Neuraminidase