title: Roles of neutrophil beta 2 integrins in kinetics of bacteremia, extravasation, and tick acquisition of Anaplasma phagocytophila in mice.
abstract: Tick saliva contains anti-inflammatory and immunosuppressive substances that facilitate blood feeding and enhance tick-vectored pathogen transmission, including Anaplasma phagocytophila an etiologic agent of granulocytic ehrlichiosis. As such, inflammation at a tick-feeding site is strikingly different than that typically observed at other sites of inflammation. Up-regulation of CD11b/CD18 occurs in host granulocytes following interaction or infection with A phagocytophila, and the absence of CD11b/CD18 results in early increases in bacteremia. We hypothesized that beta 2 integrin-dependent infection kinetics and leukocyte extravasation are important determinants of neutrophil trafficking to, and pathogen acquisition at, tick-feeding sites. A phagocytophila infection kinetics were evaluated in CD11a/CD18, CD11b/CD18, and CD18 knock-out mice using quantitative polymerase chain reaction (PCR) of blood, ticks, and skin biopsies in conjunction with histopathology. A marked increase in the rate of A phagocytophila infection of neutrophils and pathogen burden in blood followed tick feeding. Infection kinetics were modified by beta 2 integrin expression and systemic neutrophil counts. Significant neutrophil-pathogen trafficking was observed to both suture and tick sites. Despite the prominent role for beta 2 integrins in neutrophil arrest in flowing blood, successful pathogen acquisition by ticks occurred in the absence of beta 2 integrins. Establishment of feeding pools that rely less on leukocyte trafficking and more on small hemorrhages may explain the ready amplification of A phagocytophila DNA from ticks infested on CD11/CD18-deficient mouse strains.
authors.affiliation: Center for Comparative Medicine, Schools of Medicine Veterinary Medicine, University of California, Davis 95616, USA.
authors.forename: Dori L
authors.initials: DL
authors.lastname: Borjesson
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
authors.forename: Emir
authors.initials: E
authors.lastname: Hodzic
authors.forename: Hilde E V
authors.initials: HE
authors.lastname: DeCock
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Barthold
mesh_terms: D041081:Anaplasma phagocytophilum / Q000302:isolation & purification* / Q000502:physiology; D000818:Animals; D001096:Arachnid Vectors / Q000382:microbiology*; D016470:Bacteremia / Q000382:microbiology*; D040881:CD11a Antigen / Q000235:genetics; D039481:CD11b Antigen / Q000235:genetics; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D016873:Ehrlichiosis / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000382:microbiology* / Q000635:transmission; D005260:Female; D005549:Foreign-Body Reaction / Q000276:immunology; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007249:Inflammation; D018884:Ixodes / Q000382:microbiology*; D007700:Kinetics; D007958:Leukocyte Count; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016513:Mice, SCID; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology*; D012867:Skin / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D013537:Sutures; D013984:Tick Infestations / Q000150:complications / Q000382:microbiology*
chemical_list: D040881:CD11a Antigen; D039481:CD11b Antigen; D018821:CD18 Antigens