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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-04-1019.

Submitted April 9, 2002
Accepted November 25, 2002
Roles of Neutrophil 2 Integrins in Kinetics of Bacteremia, Extravasation and Tick Acquisition of Anaplasma phagocytophila in Mice
Dori L Borjesson, Scott I Simon, Emir Hodzic, Hilde E DeCock, Christie M Ballantyne, and Stephen W Barthold*
Veterinary Diagnostic Medicine, University of Minnesota, St. Paul, MN, USA; Center for Comparative Medicine, University of California, Davis, Davis, CA, USA
Biomedical Engineering, University of California, Davis, Davis, CA, USA
Center for Comparative Medicine, University of California, Davis, Davis, CA, USA
Veterinary Medicine: Pathology, Microbiology, Immunology, University of California, Davis, Davis, CA, USA
Medicine and Pediatrics, Baylor College of Medicine, Houston, TX, USA
* Corresponding author; email: swbarthold{at}ucdavis.edu.
Tick saliva contains anti-inflammatory and immunosuppressive substances that facilitate bloodfeeding and enhance tick-vectored pathogen transmission, including A. 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. Upregulation 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 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 knockout mice using quantitative 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 2 integrin expression and systemic neutrophil counts. Significant neutrophil-pathogen trafficking was observed to both suture and tick sites. Despite the prominent role for 2 integrins in neutrophil arrest in flowing blood, successful pathogen acquisition by ticks occured in the absence of 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.

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