Expression analysis of the T-cell-targeting chemokines CXCL9 and CXCL10 in mice and humans with endothelial infections caused by rickettsiae of the spotted fever group.
Rocky Mountain spotted fever and other related diseases are systemic infections caused by rickettsiae. These obligatory intracellular bacteria target the endothelium, offering an appealing model to study the interactions between endothelial cells and T lymphocytes. We investigated the mRNA expression of chemokines known to target CD8+ T cells and CD4(+) T-helper 1 cells in the lungs of C3H/HeN mice infected with Rickettsia conorii with the purpose of identifying evidence for a role of chemokines in the immune clearance of rickettsiae from the vasculature. The expression of the CXCR3 ligands CXCL9 and CXCL10 was significantly higher than the other chemokines investigated. We validated the relevance of these results in the animal model through the analysis of tissues from humans with Rocky Mountain spotted fever. We then characterized the kinetics and localization of expression of CXCL9 and CXCL10 in lungs, brain, and liver of mice infected with lethal or sublethal doses of R. conorii by a combination of quantitative real-time polymerase chain reaction and immunohistochemistry. Interestingly, the peak of expression of these chemokines occurred 4 days before CD8+ T cells infiltrated the infected tissues. Our results suggest that CXCL9 and CXCL10 may play a role early during the immune response against rickettsial infections.
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002460:Cell Line; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism*; D002648:Child; D004195:Disease Models, Animal; D004727:Endothelium / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D020114:Rickettsia conorii; D012373:Rocky Mountain Spotted Fever / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine