Effect of blocking the CXCL9/10-CXCR3 chemokine system in the outcome of endothelial-target rickettsial infections.
Rickettsiae cause systemic infections such as Rocky Mountain spotted fever and boutonneuse fever. The main cellular target of these obligately intracellular bacteria is the endothelium. T lymphocytes are the most important effectors of immunity, and the CXCR3 ligands CXCL9 and CXCL10 may play an important role in the T cell-mediated clearance of rickettsiae from the infected vasculature as suggested by recent expression studies. Here we showed that antibody-mediated neutralization of CXCL9 and CXCL10, and CXCR3 gene knockout, had no effect on survival or bacterial loads of mice infected with rickettsiae. We also demonstrated that rickettsiae triggered the endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 in vivo. These findings suggested that antigenic presentation by endothelial cells together with an endothelial inflammatory phenotype induced by the rickettsial infection may be sufficient to arrest T cells and trigger their anti-rickettsial effector mechanisms without the need for chemokines.
Valbuena
Gustavo
G
Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, USA. gvalbuen@utmb.edu
Walker
David H
DH
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001907:Boutonneuse Fever / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D002460:Cell Line; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000382:microbiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012281:Rickettsia / Q000302:isolation & purification*; D012282:Rickettsia Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D020114:Rickettsia conorii / Q000302:isolation & purification*; D013601:T-Lymphocytes / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000906:Antibodies; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1