Gene Expression Changes in the Host Response Between Resistant and Susceptible Inbred Mouse Strains After Influenza A Infection

Microbes Infect. 2010 Apr;12(4):309-18. doi: 10.1016/j.micinf.2010.01.008. Epub 2010 Jan 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Profiling*
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology*
  • Stress, Physiological*