title: Differential activation of the immune system by virulent Streptococcus pneumoniae strains determines recovery or death of the host.
abstract: Streptococcus pneumoniae infection may result in asymptomatic carriage, mucosal or invasive disease. We hypothesize that self-limiting or fatal disease outcome follows infection with S. pneumoniae differential activation of the host immune response. BALB/c and C57BL/6 mice were inoculated intranasally with S. pneumoniae serotype 3 strain WU2 and serotype 14 strain DW14 and mortality, bacterial load, pathological changes in the lungs and cytokines mRNA levels in the spleen were analysed. No differences between the C57BL/6 and the BALB/c inbred mice were observed except for the severity of their lung pathology and IL-4 expression. Infection of the two mouse strains with S. pneumoniae WU2 resulted in sepsis and death that occurred within 4 days post-inoculation. This death was preceded, in both mouse strains, in an increase over time of the lung bacterial load and bacteraemia. The lung pathology was characterized by diffuse pneumonia with marked congestion of the lungs. Analysis of mRNA expression of cytokines in the spleen revealed no alterations in tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-12 and interferon (IFN)-gamma and induction of IL-10 and IL-4. The two strains of mice survived infection with S. pneumoniae DW14. This was accompanied by a reduction over time of lung bacterial load and bacteraemia. The lung pathology was characterized by focal lymphocyte infiltration and preserved architecture of the organ. Analysis of mRNA expression of cytokines in the spleen revealed a significant decrease in the levels of TNF-alpha, TGF-beta, IL-12 and IFN-gamma mRNA expression, which usually precedes cytokine protein expression. Interestingly, a significant increase in the levels of IL-4 mRNA expression was found in BALB/c mice only. This study suggests that differential activation or evasion of cytokine expression by S. pneumoniae virulent strains determines disease outcome regardless of the host's immunogenetic background.
authors.affiliation: Ben Gurion University of the Negev, Soroka University Medical Center, Beer-Sheva, Israel. ymizr@bgumail.bgu.ac.il
authors.forename: Y
authors.initials: Y
authors.lastname: Mizrachi-Nebenzahl
authors.forename: S
authors.initials: S
authors.lastname: Lifshitz
authors.forename: R
authors.initials: R
authors.lastname: Teitelbaum
authors.forename: S
authors.initials: S
authors.lastname: Novick
authors.forename: A
authors.initials: A
authors.lastname: Levi
authors.forename: D
authors.initials: D
authors.lastname: Benharroch
authors.forename: E
authors.initials: E
authors.lastname: Ling
authors.forename: R
authors.initials: R
authors.lastname: Dagan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000235:genetics; D018450:Disease Progression; D015847:Interleukin-4 / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000502:physiology*; D014774:Virulence
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4