CCL5 regulation of mucosal chlamydial immunity and infection.
BACKGROUND
Following genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance of Chlamydia. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity against Chlamydia.


RESULTS
The present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa following Chlamydia muriduram challenge. Antibody (Ab)-mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1>Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4+ T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.


CONCLUSIONS
The suppression of these responses correlated with delayed clearance of C. muriduram, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.
Sakthivel
Senthilkumar K
SK
Emory University School of Medicine, Department of Pathology, Atlanta GA, USA. ssakthi@emory.edu
Singh
Udai P
UP
Singh
Shailesh
S
Taub
Dennis D
DD
Igietseme
Joseph U
JU
Lillard
James W
JW
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology*; D018925:Chemokines / Q000235:genetics; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007111:Immunity, Cellular; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000907:Antibodies, Bacterial; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D018925:Chemokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G