Murine model of Bartonella henselae infection in the immunocompetent host

Abstract

Bartonella henselae is an emerging pathogen causing cat scratch disease, bacillary angiomatosis, and peliosis hepatis. Progress in understanding the pathogenesis of and the immune response to these infections has been limited by the lack of an animal model. Following intraperitoneal infection of C57BL/6 mice with B. henselae, organs were cleared of cultivatable bacteria within 6 days. In contrast, B. henselae DNA could be detected in liver tissue for at least 3 months. Liver tissue showed granulomatous inflammation reaching its highest degree of intensity during the fourth week of infection and resolving within 12 weeks postinfection. This mouse model is applicable to the study of the pathogenesis of B. henselae and the immune response to this pathogen in the immunocompetent host.

FIG. 1

C57BL/6 mice were infected i.p. with B. henselae. To determine the course of infection, bacterial loads in livers and spleens were determined by culture. Nested PCR was performed with samples of B. henselae DNA from culture-negative livers. The cellular inflammatory reaction in liver tissue was quantified by counting of mononuclear foci. (A) Following i.p. inoculation with 9.1 × 10⁷ CFU of B. henselae, cultivatable organisms were cleared from livers (▾) and spleens (○) of C57BL/6 mice within 4 and 6 days, respectively (five animals per group, with each triangle or circle representing a positive culture from a single organ). DNA from B. henselae (⋆) could be detected in liver tissue for at least 3 months (with each star representing three positive results from three mice). (B) Kinetics of cellular inflammatory reaction in liver tissue following i.p. inoculation with 1.2 × 10⁸ CFU of B. henselae (three mice per group, with each circle representing a single mouse). Mononuclear foci were counted from hematoxylin-and-eosin-stained sections.

FIG. 2

Granulomatous mononuclear cell infiltration with lymphocytes and epithelioid cells in liver tissue of C57BL/6 mice at day 21 postinfection with 1.2 × 10⁸ B. henselae organisms. Sections were stained with hematoxylin and eosin (A), anti-CD4 antibody (B), and anti-CD11b antibody (C).