Open AccessThe Chemokine Receptor CXCR2 Ligand KC (CXCL1) Mediates Neutrophil Recruitment and Is Critical for Development of Experimental Lyme Arthritis and Carditis
Author(s) -
Anna M. Ritzman,
Jennifer M. Hughes-Hanks,
Victoria A. Blaho,
Laura E. Wax,
William J. Mitchell,
Charles R. Brown
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00798-10
Subject(s) - cxcl1 , borrelia burgdorferi , cxcl2 , carditis , arthritis , immunology , cxc chemokine receptors , chemokine , biology , chemokine receptor , lyme disease , ccr2 , inflammation , antibody
Deletion of the chemokine receptor CXCR2 prevents the recruitment of neutrophils into tissues and subsequent development of experimental Lyme arthritis. Following footpad inoculation ofBorrelia burgdorferi , the agent of Lyme disease, expression of the CXCR2 ligand KC (CXCL1) is highly upregulated in the joints of arthritis-susceptible mice and is likely to play an important role in the recruitment of neutrophils to the site of infection. To test this hypothesis, we infected C3H KC−/− mice withB. burgdorferi and followed the development of arthritis and carditis. Ankle swelling was significantly attenuated during the peak of arthritis in the KC−/− mice. Arthritis severity scores were significantly lower in the KC−/− mice on days 11 and 21 postinfection, with fewer neutrophils present in the inflammatory lesions. Cardiac lesions were also significantly decreased in KC−/− mice at day 21 postinfection. There were, however, no differences between C3H wild-type and KC−/− mice in spirochete clearance from tissues. Two other CXCR2 ligands, LIX (CXCL5) and MIP-2 (CXCL2), were not increased to compensate for the loss of KC, and the production of several innate cytokines was unaltered. These results demonstrate that KC plays a critical nonredundant role in the development of experimental Lyme arthritis and carditis via CXCR2-mediated recruitment of neutrophils into the site of infection.