title: CCL2 expression is mediated by type I IFN receptor and recruits NK and T cells to the lung during MVA infection.
abstract: Migration of leukocytes to the site of microbial infection is important for the development of effective host immunity. Recombinant modified vaccinia virus Ankara is frequently used as a viral vector vaccine in preclinical and clinical studies. In comparison to other vaccinia virus strains, modified vaccinia virus Ankara robustly induces chemokine expression and rapid attraction of leukocytes. In particular, chemokine (C-C motif) ligand 2 (CCL2) has been shown to be critical for leukocyte recruitment to the lung. In this study, MVA-induced CCL2 expression in murine macrophages was dependent on type I interferon receptor and not Toll-like receptor-2. The critical role of type I interferon receptor signaling for CCL2 production in the lung was confirmed in type I interferon receptor-deficient mice (Ifnar1(-/-)). In addition, comparing Ifnar1(-/-) and Ccl2(-/-) mice with wild-type mice, we observed a similar impairment in the recruitment of natural killer and T cells to the lung after intranasal infection with modified vaccinia virus Ankara. Conversely, neutrophil recruitment was not affected in Ifnar1(-/-) and Ccl2(-/-) mice. We conclude that type I interferons, besides their known antiviral properties, can initiate the recruitment and activation of leukocytes via induction of chemokine expression including CCL2.
authors.affiliation: Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Munich, Germany; Division of Virology, Paul-Ehrlich-Institut, Langen, Germany; and michael.lehmann@lmu.de.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Lehmann
authors.affiliation: Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Munich, Germany;
authors.forename: Lino E
authors.initials: LE
authors.lastname: Torres-Domínguez
authors.affiliation: Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Munich, Germany;
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Price
authors.affiliation: Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Munich, Germany;
authors.forename: Christine
authors.initials: C
authors.lastname: Brandmüller
authors.affiliation: Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.affiliation: Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, Munich, Germany;
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000821:virology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000473:pathology; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000821:virology*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D018932:Chemokine CCL2; D007370:Interferon Type I; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D053633:Receptor, Interferon alpha-beta
keywords: cell migration; chemokine; interferon; lung; vaccinia virus