The innate immune response to Streptococcus pneumoniae in the lung depends on serotype and host response

Beza Seyoum, Masahide Yano, Liise anne Pirofski

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Bacteremic pneumonia with some pneumococcal capsular serotypes, including serotype 3 (ST3), has been associated with a higher risk of death, whereas others, such as ST8, are associated with a lower risk. To provide a molecular basis for understanding such differences, we used oligo cDNA microarrays to analyze and compare the gene expression profiles of the lungs of Balb/c mice infected intranasally with either ST3, strain A66.1, or ST8, strain ATCC 6308 (6308). Compared to uninfected controls, infection with either A66.1 or 6308 led to inoculum-dependent expression of IFN-γ inducible CXC chemokines among other pro-inflammatory genes. To investigate the role that IFN-γ inducible chemokines CXCL9, CXCL10 and CXCL11 play in A66.1- and 6308-induced pneumonia, we examined the effect of the absence of their common receptor, CXCR3, on intranasal infection in CXCR3 -/- (Balb/c) mice. Compared to wild type (WT) mice, virulence of A66.1 but not 6308 was attenuated in CXCR3 -/- mice. A66.1-infected CXCR3 -/- mice had fewer lung neutrophils and more alveolar macrophages 48h after infection and fewer blood CFU 72h after infection. Histopathological examination of lung sections revealed less inflammation among A66.1-infected CXCR3 -/- than WT mice. The reduced virulence of A66.1 in CXCR3 -/- mice suggests that inhibition of the functional activity of IFN-γ inducible chemokines modulates the host response to A66.1, in turn suggesting a novel approach to improve vaccine-mediated protection against ST3 pneumonia.

Original languageEnglish (US)
Pages (from-to)8002-8011
Number of pages10
JournalVaccine
Volume29
Issue number45
DOIs
StatePublished - Oct 19 2011

Keywords

  • CXCR3
  • IFN-γ inducible chemokines
  • Inflammation
  • Pneumococcal pathogenesis
  • Serotype 3 pneumococcus
  • Serotype 8 pneumococcus

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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