CXCL16 regulates cell-mediated immunity to Salmonella enterica serovar Enteritidis via promotion of gamma interferon production.
CXCL16 is a recently discovered multifaceted chemokine that has been shown not only to recruit activated T lymphocytes but also to play a direct role in the binding and phagocytosis of bacteria by professional antigen-presenting cells. In this study, we investigated the role of CXCL16 in vivo in the regulation of the immune response using a murine model of Salmonella enterica serovar Enteritidis infection. The expression of CXCL16 was strongly upregulated in the spleens and livers of animals developing an immune response to a primary acute infection but not in the Peyer's patches. Animals developing a secondary response after reexposure to the bacteria displayed a similar pattern of expression. During the primary response, prior treatment with neutralizing antibodies to CXCL16 induced a significant increase in bacterial burden in the spleen and liver. The production of gamma interferon (IFN-gamma) by the lymphocytes in the spleen was decreased by anti-CXCL16 treatment. In comparison, during the secondary response, anti-CXCL16 treatment also significantly increased bacterial burden in both the spleen and liver but had no effect on IFN-gamma production. No role was found for CXCL16 in the production of antibody against SefA, a major surface antigen of S. enteritidis. Together, these results demonstrate a role for CXCL16 in the control of bacterial colonization of target organs and, more specifically, in the regulation of the cell-mediated arm of the primary response to S. enteritidis.
Fahy
Olivier L
OL
Department of Molecular and Biomedical Science, The University of Adelaide, North Terrace Campus, Adelaide, SA 5005, Australia.
Townley
Scott L
SL
McColl
Shaun R
SR
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology*; D012477:Salmonella enteritidis; D015854:Up-Regulation
D019138:Antibodies, Blocking; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; C515203:Cxcl11 protein, mouse; C498926:Cxcl16 protein, mouse; C485969:Cxcl9 protein, mouse; D051116:Receptors, Scavenger; D007371:Interferon-gamma