Analysis of the lung transcriptome in Mycobacterium tuberculosis-infected mice reveals major differences in immune response pathways between TB-susceptible and resistant hosts

Tuberculosis (Edinb). 2013 Mar;93(2):263-9. doi: 10.1016/j.tube.2012.11.007. Epub 2012 Dec 29.

Abstract

Using whole genome microarrays, we compared changes in gene expression patterns in the lungs of TB-resistant A/Sn and TB-susceptible I/St mice at day 14 following infection with Mycobacterium tuberculosis H37Rv. Analyses of differentially expressed genes for representation of gene ontology terms and activation of regulatory pathways revealed interstrain differences in antigen presentation, NK, T and B cell activation pathways. In general, resistant A/Sn mice exhibited a more complex pattern and stronger activation of host defense pathways compared to the TB-susceptible I/St mouse strain. In addition, in I/St mice elevated activation of genes involved in neutrophil response was observed and confirmed by quantitative RT-PCR and histopathology. Furthermore, a specific post infection upregulation of cysteine protease inhibitors was found in susceptible I/St mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Disease Models, Animal
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / immunology
  • Genetic Predisposition to Disease
  • Granulocytes / immunology
  • Lung / immunology*
  • Male
  • Mice
  • Mice, Inbred A
  • Mice, Inbred Strains
  • Neutrophil Infiltration / genetics
  • Salivary Cystatins / biosynthesis
  • Salivary Cystatins / genetics
  • Species Specificity
  • Transcriptome / immunology*
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / immunology*
  • Up-Regulation / immunology

Substances

  • Salivary Cystatins