title: Cytomegalovirus infection enhances the immune response to influenza.
abstract: Cytomegalovirus (CMV) is a β-herpesvirus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli, and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV status. In contrast, CMV-seropositive young adults exhibited enhanced antibody responses to influenza vaccination, increased CD8(+) T cell sensitivity, and elevated levels of circulating interferon-γ compared to seronegative individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the ubiquity of CMV infection in humans and many other species.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA. mdavis@cmgm.stanford.edu furmand@stanford.edu.
authors.forename: David
authors.initials: D
authors.lastname: Furman
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jojic
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Immunology, Rappaport Institute of Medical Research, Faculty of Medicine and Faculty of Biology, Technion, Haifa 32000, Israel.
authors.forename: Shai S
authors.initials: SS
authors.lastname: Shen-Orr
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Cesar J L
authors.initials: CJ
authors.lastname: Angel
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Suna
authors.initials: S
authors.lastname: Onengut-Gumuscu
authors.affiliation: Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kidd
authors.affiliation: Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Holden T
authors.initials: HT
authors.lastname: Maecker
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA. Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA. Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA. The Howard Hughes Medical Institute. mdavis@cmgm.stanford.edu furmand@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology; D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection / Q000187:drug effects / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D005260:Female; D006801:Humans; D007109:Immunity; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology*; D007371:Interferon-gamma / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D018146:Muromegalovirus / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013997:Time Factors; D014611:Vaccination; D019562:Viral Load; D055815:Young Adult
chemical_list: D018106:CD28 Antigens; D007371:Interferon-gamma
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