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

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 (C5713L/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 D13A/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 (C) 2010 Elsevier Masson SAS All rights reserved.