Beta2 integrins control the severity of murine Lyme carditis.
Infection of C57BL/6 (B6) mice with the Lyme disease spirochete Borrelia burgdorferi can result in development of arthritis and carditis. B. burgdorferi induces expression of beta2/CD18 integrins, adhesion molecules that mediate the firm adhesion of leukocytes to the endothelium necessary for cellular extravasation during inflammation. The important role of beta2/CD18 integrins during extravasation suggests that these molecules play a role in the development of Lyme arthritis and carditis. The dependency of these inflammatory processes on the beta2 integrins was investigated in CD18 hypomorph mice, which express low levels of CD18. The results indicate that CD18 deficiency did not abrogate development of Lyme arthritis or carditis. Moreover, it resulted in increased severity of Lyme carditis. B. burgdorferi-infected CD18 hypomorph mice showed an increased macrophage infiltration of the heart, while they produced lower levels of borreliacidal anti-B. burgdorferi antibodies compared to wild-type mice. In accordance with these results, we demonstrate that dendritic cells from CD18 hypomorph mice secrete higher levels of monocyte/macrophage chemoattractant protein 1 (MCP-1/CCL2) in response to B. burgdorferi. Similarly, we show by real-time PCR that B. burgdorferi-infected hearts from CD18 hypomorph mice express increased levels of MCP-1 RNA compared to wild-type mice. Overall, our results indicate that beta2 integrin deficiency does not abrogate B. burgdorferi-induced inflammation; rather, it results in increased recruitment of macrophages into the B. burgdorferi-infected heart, likely due to the increased expression of MCP-1 in this tissue. Thus, beta2 integrins may play a regulatory role in B. burgdorferi-induced inflammation beyond mediating adhesion of leukocytes to the endothelium.
Guerau-de-Arellano
Mireia
M
Department of Pathology, Tufts University School of Medicine, Jaharis 512, 150 Harrison Ave., Boston, MA 02111, USA.
Alroy
Joseph
J
Huber
Brigitte T
BT
D000818:Animals; D001770:Blood Bactericidal Activity; D018821:CD18 Antigens / Q000502:physiology*; D018932:Chemokine CCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology; D008193:Lyme Disease / Q000150:complications* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000209:etiology*; D009206:Myocardium / Q000473:pathology
D018821:CD18 Antigens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2