Lymphadenopathy in a novel mouse model of Bartonella-induced cat scratch disease results from lymphocyte immigration and proliferation and is regulated by interferon-alpha/beta.
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. Carboxyfluorescein- and 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-alpha/beta-receptor I chain-deficient mice revealed that interferon-alpha/beta 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.
Kunz
Stefanie
S
Immunologie und Hygiene, Universitätsklinikum Erlangen, Wasserturmstrasse 3-5, Erlangen, Germany.
Oberle
Karin
K
Sander
Anna
A
Bogdan
Christian
C
Schleicher
Ulrike
U
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D001473:Bartonella / Q000502:physiology*; D002372:Cat-Scratch Disease / Q000276:immunology / Q000382:microbiology*; D002465:Cell Movement; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D007121:Immunocompetence; D007249:Inflammation; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008206:Lymphatic Diseases / Q000276:immunology* / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D016898:Interferon-alpha; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta