Pneumococcal behavior and host responses during bronchopneumonia are affected differently by the cytolytic and complement-activating activities of pneumolysin - PubMed (original) (raw)

Pneumococcal behavior and host responses during bronchopneumonia are affected differently by the cytolytic and complement-activating activities of pneumolysin

Rania Jounblat et al. Infect Immun. 2003 Apr.

Erratum in

Abstract

Pneumolysin, a multifunctional toxin produced by all clinical isolates of Streptococcus pneumoniae, is strongly implicated in the pathogenesis of pneumococcal bronchopneumonia and septicemia. Using isogenic mutant strains, we examined the effect of deletion of the cytotoxic activity or complement-activating activity of pneumolysin on bacterial growth in lungs and blood, histological changes in infected lung tissue, and the pattern of inflammatory cell recruitment. Both of the activities of pneumolysin contributed to the pathology in the lungs, as well as the timing of the onset of bacteremia. Histological changes in the lungs were delayed after infection with either mutant compared to the changes seen after infection with the wild-type pneumococcus. The complement-activating activity of pneumolysin affected the accumulation of T cells, whereas the toxin's cytolytic activity influenced neutrophil recruitment into lung tissue.

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Figures

FIG. 1.

FIG. 1.

Time courses for changes in the numbers of the S. pneumoniae wild-type (□), H+/C− (⋄), and H2−/C+ (○) strains in the lungs of MF1 mice infected intranasally with 106 CFU (n = 10 for each time point). The error bars indicate standard errors of the means. An asterisk indicates that the P value is <0.05 for a comparison of the H+/C− or H2−/C+ mutant with the wild-type strain.

FIG. 2.

FIG. 2.

Time courses for changes in the numbers of the S. pneumoniae wild-type (□), H+/C− (⋄), and H2−/C+ (○) strains in the blood of MF1 mice infected intranasally with 106 CFU (n = 10 for each time point). The error bars indicate standard errors of the means. An asterisk indicates that the P value is <0.05 for a comparison of the H+/C− or H2−/C+ mutant with the wild-type strain.

FIG. 3.

FIG. 3.

Light microscopy of lung tissue from a mouse infected with 106 CFU of S. pneumoniae H+/C− at 24 h postinfection (A), from a mouse infected with 106 CFU of S. pneumoniae H2−/C+ at 24 h postinfection (B), from a mouse infected with 106 CFU of S. pneumoniae H+/C− at 48 h postinfection (C), and from a mouse infected with 106 CFU of S. pneumoniae H2−/C+ at 48 h postinfection (D). In panel A the double arrows indicate heavy cellular infiltrate in infected bronchioles. In panel B the single arrows indicate slight cellular infiltration of infected bronchioles. In panels A and B the open arrows indicate general lung parenchyma that was not involved in inflammation. In panels C and D the thin arrows indicate hypertrophy of the inflamed bronchiole walls, the arrowheads indicate severe multifocal peribronchial infiltration of inflammatory cells, and the thick arrows indicate extensive infiltration of lung parenchyma. Magnification, ×250.

FIG. 3.

FIG. 3.

Light microscopy of lung tissue from a mouse infected with 106 CFU of S. pneumoniae H+/C− at 24 h postinfection (A), from a mouse infected with 106 CFU of S. pneumoniae H2−/C+ at 24 h postinfection (B), from a mouse infected with 106 CFU of S. pneumoniae H+/C− at 48 h postinfection (C), and from a mouse infected with 106 CFU of S. pneumoniae H2−/C+ at 48 h postinfection (D). In panel A the double arrows indicate heavy cellular infiltrate in infected bronchioles. In panel B the single arrows indicate slight cellular infiltration of infected bronchioles. In panels A and B the open arrows indicate general lung parenchyma that was not involved in inflammation. In panels C and D the thin arrows indicate hypertrophy of the inflamed bronchiole walls, the arrowheads indicate severe multifocal peribronchial infiltration of inflammatory cells, and the thick arrows indicate extensive infiltration of lung parenchyma. Magnification, ×250.

FIG. 4.

FIG. 4.

Numbers of neutrophils (□), macrophages (⋄), T cells (○), and B cells (▵) in tissue sections from lungs of MF1 mice infected intranasally with 106 CFU of the S. pneumoniae wild-type strain (A), with 106 CFU of S. pneumoniae H+/C− (B), and with 106 CFU of S. pneumoniae H2−/C+ (C) (n = 4 for each time point) The error bars indicate standard errors of the means.

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References

    1. Alcantra, R. B., L. Preheim, and M. J. Gentry. 1999. Role of pneumolysin's complement-activating activity during pneumococcal bacteremia in cirrhotic rats. Infect. Immun. 67:2862-2866. - PMC - PubMed
    1. Alexander, J. E., A. M. Berry, J. C. Paton, J. B. Rubins, P. W. Andrew, and T. J. Mitchell. 1998. Amino acid changes affecting the activity of pneumolysin alter the behaviour of pneumococci in pneumonia. Microb. Pathog. 24:167-174. - PubMed
    1. Baba, H., I. Kawamura, C. Kohda, T. Nomura, Y. Ito, T. Kimoto, I. Watanabe, S. Ichiyama, and M. Mitsuyama. 2002. Induction of gamma interferon and nitric oxide by truncated pneumolysin that lacks pore-forming activity. Infect. Immun. 70:107-113. - PMC - PubMed
    1. Benton, K. A., J. C. Paton, and D. E. Briles. 1997. The hemolytic and complement activating properties of pneumolysin do not contribute individually to virulence in a pneumococcal bacteremia model. Microb. Pathog. 23:201-209. - PubMed
    1. Berry, A. M., J. E. Alexander, T. J. Mitchell, P. W. Andrew, D. Hansman, and J. C. Paton. 1995. Effect of defined point mutations in the pneumolysin gene on the virulence of Streptococcus pneumoniae. Infect. Immun. 63:1969-1974. - PMC - PubMed

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