Genetic basis of murine antibacterial defense to streptococcal lung infection

John W. Hollingsworth, Gregory Whitehead, Katherine Gray Berman, Erin McElvania Tekippe, M. Ian Gilmour, Jennie E. Larkin, John Quackenbush, David A. Schwartz

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

To evaluate the effect of genetic background on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6tlr2-/-) were infected with three doses of Streptococcus zooepidemicus (500, 5,000, or 50,000 colony-forming units) by alveolar challenge. There was a range of susceptibility between the strains at each dose and time point (6, 24, and 96 h). At the lowest dose, the 129/SvImJ and C3H/HeJ strains had significantly higher bacterial counts at all time points after infection, when compared to A/J, DBA/2J, CAST/Ei, FVB/NJ, which were resistant to infection at the low dose of innoculum. At the medium dose, 129/SvImJ and C3H/HeJ had higher bacterial counts, while A/J, DBA/2J, and BALB/cJ showed reduced streptococcal growth. After the highest dose of Streptococcus, there were minimal differences between strains, suggesting the protective impact of modifier genes can be overcome. TLR2-deficient animals contained increased bacterial load with reduced cytokines after 96 h when compared to C57BL/6J controls suggesting a role of innate immunity in late antibacterial defense. Overall, we identify vulnerable (129/SvlmJ and C3H/HeJ) and resistant (A/J, FVB, and DBA) mouse strains to streptococcal lung infection, which demonstrate divergent genetic expression profiles. These results demonstrate that innate differences in pulmonary host defense to S. zooepidemicus are dependent on host genetic factors.

Original languageEnglish (US)
Pages (from-to)713-724
Number of pages12
JournalImmunogenetics
Volume59
Issue number9
DOIs
StatePublished - Sep 1 2007

Keywords

  • Innate immunity
  • Interstrain differences
  • Lung
  • Streptococcus zooepidemicus
  • tlr2
  • tlr4

ASJC Scopus subject areas

  • Immunology
  • Genetics

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