Lymphadenopathy in a Novel Mouse Model of Bartonella-Induced Cat Scratch Disease Results from Lymphocyte Immigration and Proliferation and Is Regulated by Interferon-α/β

Abstract

In immunocompetent humans, cat scratch disease (CSD) is elicited by the Gram-negative bacterium Bartonella henselae and is characterized by a benign regional lymphadenopathy, the pathogenesis of which is poorly understood. Here, we describe a novel mouse model of Bartonella-induced CSD-like disease that allowed us to investigate the mechanisms leading to lymphadenopathy in vivo. In wild-type mice, a subcutaneous inoculation of either viable or inactivated B. henselae led to a strong swelling of the draining lymph node, which was long-lasting despite the rapid elimination of the bacteria. Carboxyfluoresceinand bromodesoxyuridine-labeling experiments showed that lymph node enlargement resulted from modified immigration and enhanced proliferation of lymphocytes, preferentially of B cells. A comparative analysis of B. henselae and the rodent pathogen B. grahamii in wild-type versus interferon-␣/␤-receptor I chaindeficient mice revealed that interferon-␣/␤ is not only differentially induced by these two Bartonella species but also exerts an inhibitory effect on the development of lymphadenopathy both in vitro and in vivo. These data demonstrate that the lymphadenopathy of human CSD can be reproduced and studied in a mouse model and provide the first insights into the underlying immunological mechanisms.

Intruders below the Radar: Molecular Pathogenesis of Bartonella spp

“…The characteristic swelling of lymph nodes derives from the formation of B-cellrich granulomas that apparently feature continuous recruitment and stimulation of macrophages (397,431). Similar lymphadenopathy could be observed in a mouse model for cat scratch disease, though no granuloma formation was evident and the swelling was mostly caused by the immigration and proliferation of B cells (244). Interestingly, the use of B. grahamii (infecting mice as its reservoir host) instead of B. henselae in the same study did not result in comparable lymphadenopathy unless the bacteria were sonicated before inoculation, though infecting IFN-␣/␤ receptordeficient mice yielded lymphadenopathy with both Bartonella species.…”

Bartonella spp.: Throwing light on uncommon human infections

“…However, due to the intraperitoneal infection route, this model cannot mimick the natural course of CSD. A subcutaneous infection model of C57BL/6 or BALB/c mice (Kunz et al, 2008) seems to be more realistic: Here, a B. henselae infection resulted in a strong swelling of the draining lymph node strongly resembling CSD. Similar to human disease, this swelling was due to the enhanced proliferation of lymphocytes (preferentially B cells).…”

BartonellaInfection in Rodents and Their Flea Ectoparasites: An Overview

“…It is noteworthy in these cases that bacteremia was not established (Regnath et al 1998, Kunz et al 2008.…”