Analysis of murine genetic predisposition to pneumococcal infection reveals a critical role of alveolar macrophages in maintaining the sterility of the lower respiratory tract

Keer Sun, Yan Gan, Dennis W. Metzger

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The study of pathogenic mechanisms of disease can be greatly facilitated by studying genetic differences in susceptibility to infection. In the present study, we compared the severity of pneumococcal infection in C57BL/6 (B6) and 129Sv mice. The results showed that 129Sv mice were remarkably more susceptible to pneumococcal infection than B6 mice. Bacterial clearance, proinflammatory mediators, leukocyte recruitment, and phagocyte activities were measured to examine potential immune factors associated with differences in susceptibility to pneumococcal infection. The greater susceptibility of 129Sv mice was associated only with inadequate alveolar macrophage bacterial killing, as indicated by significantly decreased initial bacterial clearance from the respiratory tract. Effective pneumococcal clearance was not dependent upon Toll-like receptor 2 (TLR2) expression, oxidative stress, or matrix metallopeptidase 12 (MMP-12) expression. Furthermore, phagocytosis analysis suggested that the deficiency found in 129Sv alveolar macrophages was not due to a lack of bacterial recognition but, rather, to reduced bacterial uptake. In conclusion, our findings indicate a crucial role of alveolar macrophage phagocytosis during innate defense against pneumococcal infection, which may explain the association of host genetic risk factors with predisposition to pneumococcal infection.

Original languageEnglish (US)
Pages (from-to)1842-1847
Number of pages6
JournalInfection and immunity
Volume79
Issue number5
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Analysis of murine genetic predisposition to pneumococcal infection reveals a critical role of alveolar macrophages in maintaining the sterility of the lower respiratory tract'. Together they form a unique fingerprint.

Cite this