SUMMARYStreptococcus 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)-α , transforming growth factor (TGF)-β , interleukin (IL)-12 and interferon (IFN)-γ 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-α , TGF-β , IL-12 and IFN-γ 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.
The interaction between Streptococcus pneumoniae (S. pneumoniae) and the mucosal epithelial cells of its host is a prerequisite for pneumococcal disease development, yet the specificity of this interaction between different respiratory cells is not fully understood. In the present study, three areas were examined: i) The capability of the encapsulated S. pneumoniae serotype 3 strain (WU2) to adhere to and invade primary nasal-derived epithelial cells in comparison to primary oral-derived epithelial cells, A549 adenocarcinoma cells and BEAS-2B viral transformed bronchial cells; ii) the capability of the unencapsulated 3.8DW strain (a WU2 derivative) to adhere to and invade the same cells over time; and iii) the ability of various genetically-unrelated encapsulated and unencapsulated S. pneumoniae strains to adhere to and invade A549 lung epithelial cells. The results of the present study demonstrated that the encapsulated WU2 strain adhesion to and invasion of primary nasal epithelial cells was greatest, followed by BEAS-2B, A549 and primary oral epithelial cells. By contrast, the unencapsulated 3.8-DW strain invaded oral epithelial cells significantly more efficiently when compared to the nasal epithelial cells. In addition, unencapsulated S. pneumoniae strains adhered to and invaded the A459 cells significantly more efficiently than the encapsulated strains; this is consistent with previously published data. In conclusion, the findings presented in the current study indicated that the adhesion and invasion of the WU2 strain to primary nasal epithelial cells was more efficient compared with the other cultured respiratory epithelial cells tested, which corresponds to the natural course of S. pneumoniae infection and disease development. The target cell preference of unencapsulated strains was different from that of the encapsulated strains, which may be due to the exposure of cell wall proteins.
Mice were inoculated intranasally with Streptococcus pneumoniae isolates of serotype 14 with different genetic backgrounds (14R, 14DW) and a capsular switch of 14R, strain 9VR (serotype 9V). Inoculation of the mice with 14R and 9VR resulted in 60% mortality. All the mice survived 14DW inoculation. No differences in lungs' bacterial loads were found 3 h following inoculation. Bacterial clearance of 5 logs was observed 48 h after inoculation with 14DW versus within 1 log 48 h after inoculation with 14R and 9VR. No significant differences in bacterial size or the capsular amount could be found between 14R and 14DW. We conclude that factor(s) in addition to the capsule, contribute to disease outcome.
SUMMARY Vulnerability to Streptococcus pneumoniae is most pronounced in children. The microbial virulence factors and the features of the host immune response contributing to this phenomenon are not completely understood. In the current study, the humoral immune response to separated Strep. pneumoniae surface proteins and the ability to interfere with Strep. pneumoniae adhesion to cultured epithelial cells were analysed in adults and in children. Sera collected from healthy adults recognized Strep. pneumoniae separated lectin and nonlectin surface proteins in Western blot analysis and inhibited on average 80% of Strep. pneumoniae adhesion to epithelial cells in a concentration‐dependent manner. However, sera longitudinally collected from healthy children attending day care centres from 18 months of age and over the course of the following 2 years revealed: (a) development of antibodies to previously unrecognized Strep. pneumoniae surface proteins with age; (b) a quantitative increase in antibody responses, measured by densitometry, towards separated Strep. pneumoniae surface proteins with age; and (c) inhibition of Strep. pneumoniae adhesion to epithelial cells, which was 50% on average at 18 months of age, increased significantly to an average level of 80% inhibition at 42 months of age equalling adult sera inhibitory values. The results obtained in the current study, from the longitudinally collected sera from healthy children with documented repeated Strep. pneumoniae colonization, show that repeated exposures are insufficient to elicit an immune response to Strep. pneumoniae proteins at 18 months of age. This inability to recognize Strep. pneumoniae surface proteins may stem from the inefficiency of T‐cell‐dependent B‐cell responses at this age and/or from the low immunogenicity of the proteins.
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