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 Citations (Scopus)

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

Fingerprint

Streptococcus pneumoniae
Innate Immunity
serotypes
lungs
Lung
mice
pneumonia
Pneumonia
Virulence
Chemokine CXCL11
Chemokine CXCL9
CXCR3 Receptors
virulence
Infection
infection
Chemokine CXCL10
CXC Chemokines
Alveolar Macrophages
chemokines
Microarray Analysis

Keywords

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

ASJC Scopus subject areas

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

Cite this

The innate immune response to Streptococcus pneumoniae in the lung depends on serotype and host response. / Seyoum, Beza; Yano, Masahide; Pirofski, Liise-anne.

In: Vaccine, Vol. 29, No. 45, 19.10.2011, p. 8002-8011.

Research output: Contribution to journalArticle

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