title: Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice.
abstract: Influenza A virus replicates in the respiratory epithelium and induces an inflammatory infiltrate comprised of mononuclear cells and neutrophils. To understand the development of the cell-mediated immune response to influenza and how leukocyte trafficking to sites of inflammation is regulated, we examined the chemokine expression pattern in lung tissue from A/PR/8/34-infected C57BL/6 mice using an RNase protection assay. Monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-3alpha, regulated on activation, normal T expressed and secreted (RANTES), MIP-2, and interferon-inducible protein 10 (IP-10) mRNA expression was up-regulated between days 5 and 15 after infection, consistent with a role for these chemokines in leukocyte recruitment to the lung. Low levels of expression were detected for the CC chemokine receptors (CCR)2 and CCR5, whereas CXC chemokine receptor (CXCR)3 was significantly up-regulated by day 10 after infection, coinciding with peak inflammatory cell infiltration in the airways. As RANTES, IP-10, and their receptors were up-regulated during influenza virus infection, we investigated leukocyte recruitment and viral clearance in mice deficient in RANTES or CXCR3, the receptor for IP-10. Leukocyte recruitment and viral replication in influenza-infected RANTES knockout(-/-) mice were similar to that in control mice, showing that RANTES is not essential for the immune response to influenza infection. Similarly, leukocyte recruitment and viral replication in CXCR3-/- mice were identical to control mice, except at day 8 postinfection, where fewer lymphocytes, neutrophils, and eosinophils were detected in the bronchoalveolar lavage of CXCR3-/- mice. These studies suggest that although the chemokines detected may play a role in regulating leukocyte trafficking to the lung during influenza infection, some may be functionally redundant.
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, CA, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wareing
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Lyon
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Sally R
authors.initials: SR
authors.lastname: Sarawar
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054418:Chemokine CCL20; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D009980:Influenza A virus / Q000472:pathogenicity; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D014779:Virus Replication
chemical_list: C486997:Ccl20 protein, rat; D054418:Chemokine CCL20; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054426:Chemokine CXCL2; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C404915:Cxcl2 protein, mouse; C515188:Cxcr3 protein, mouse; C515189:Cxcr3 protein, rat; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D012260:Ribonucleases