title: The innate immune response to Streptococcus pneumoniae in the lung depends on serotype and host response.
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 48 h after infection and fewer blood CFU 72 h 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.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Beza
authors.initials: B
authors.lastname: Seyoum
authors.forename: Masahide
authors.initials: M
authors.lastname: Yano
authors.forename: Liise-anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity*; D013997:Time Factors
chemical_list: D018925:Chemokines