Tick saliva contains anti-inflammatory and immunosuppressive substances that facilitate blood feeding and enhance tickvectored pathogen transmission, including Anaplasma phagocytophila, an etiologic agent of granulocytic ehrlichiosis. As such, inflammation at a tickfeeding 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 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 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 occurred 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. (Blood.