title: Gene expression changes in the host response between resistant and susceptible inbred mouse strains after influenza A infection.
abstract: Inbred mouse strains exhibit differences in susceptibility to influenza A infections. However, the molecular mechanisms underlying these differences are unknown. Therefore, we infected a highly susceptible mouse strain (DBA/2J) and a resistant strain (C57BL/6J) with influenza A H1N1 (PR8) and performed genome-wide expression analysis. We found genes expressed in lung epithelium that were specifically down-regulated in DBA/2J mice, whereas a cluster of genes on chromosome 3 was only down-regulated in C57BL/6J. In both mouse strains, chemokines, cytokines and interferon-response genes were up-regulated, indicating that the main innate immune defense pathways were activated. However, many immune response genes were up-regulated in DBA/2J much stronger than in C57BL/6J, and several immune response genes were exclusively regulated in DBA/2J. Thus, susceptible DBA/2J mice showed a hyper-inflammatory response. This response is similar to infections with highly pathogenic influenza virus and may serve as a paradigm for a hyper-inflammatory host response to influenza A virus.
authors.affiliation: Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Rudi
authors.initials: R
authors.lastname: Alberts
authors.forename: Barkha
authors.initials: B
authors.lastname: Srivastava
authors.forename: Haiya
authors.initials: H
authors.lastname: Wu
authors.forename: Nuno
authors.initials: N
authors.lastname: Viegas
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Frank
authors.initials: F
authors.lastname: Klawonn
authors.forename: Natalia
authors.initials: N
authors.lastname: Novoselova
authors.forename: Tania Zaverucha
authors.initials: TZ
authors.lastname: do Valle
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Panthier
authors.forename: Klaus
authors.initials: K
authors.lastname: Schughart
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology*; D013312:Stress, Physiological