• Gene expression changes in the host response between resistant and susceptible inbred mouse strains after influenza A infection.

      Alberts, Rudi; Srivastava, Barkha; Wu, Haiya; Viegas, Nuno; Geffers, Robert; Klawonn, Frank; Novoselova, Natalia; do Valle, Tania Zaverucha; Panthier, Jean-Jacques; Schughart, Klaus; Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany. (2010-04)
      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.