title: CXCR3-deficiency protects influenza-infected CCR5-deficient mice from mortality.
abstract: Mice lacking the chemokine receptor CCR5 are susceptible to mortality from a normally non-lethal influenza infection. Here we found that CXCR3-deficiency rescued CCR5-deficient (CCR5(-/-)) mice from influenza-induced mortality. The number of mononuclear phagocytes in the airways was transiently increased in CCR5(-/-) mice but not in CXCR3-CCR5 double-deficient mice. Antigen-specific CXCR3-CCR5 double-deficient CD8 effector cells were less efficient at entering the airways compared with WT or CCR5(-/-) CD8 effector cells. The decrease in inflammatory cell infiltrates in CXCR3-CCR5 double-deficient-infected mice correlated with a decrease in CCL2 and IFN-gamma production in the airways. Finally, CXCR3-CCR5 double-deficient mice that survived the primary viral challenge were protected from a lethal secondary challenge, indicating that T-cell-mediated protective memory was not compromised in mice lacking these chemokine receptors. In conclusion, CXCR3-deficiency attenuated the lethal cellular immune response in CCR5(-/-) influenza-infected mice without hindering viral clearance or long-term immunity.
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Shaza A
authors.initials: SA
authors.lastname: Fadel
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Bromley
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D005260:Female; D009980:Influenza A virus / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015996:Survival Rate
chemical_list: C515188:Cxcr3 protein, mouse; D019713:Receptors, CCR5; D054367:Receptors, CXCR3