Streptococcus pneumoniae is a Gram-positive bacterial pathogen that colonizes the mucosal surfaces of the host nasopharynx and upper airway. Through a combination of virulence-factor activity and an ability to evade the early components of the host immune response, this organism can spread from the upper respiratory tract to the sterile regions of the lower respiratory tract, which leads to pneumonia. In this Review, we describe how S. pneumoniae uses its armamentarium of virulence factors to colonize the upper and lower respiratory tracts of the host and cause disease.

The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease.

Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines.

The pneumococcus undergoes spontaneous phase variation between an opaque and a transparent colony form. In an animal model of systemic infection following intraperitoneal inoculation of mice, the opaque phenotype was significantly more virulent than the transparent for each of 3 strains examined. The opaque phenotype was associated with 1.2- to 5.6-fold greater amounts of capsular polysaccharide compared with the transparent using a sandwich ELISA. A similar technique comparing the amount of total teichoic acid showed that the transparent phenotype had 2.1- to 3.8-fold more immunodetectable teichoic acid. This difference was confirmed by comparing the incorporation of [3H]choline into teichoic acid. Cell fractionation revealed that variation in quantity of incorporated choline was due to differences in cell wall-associated teichoic acid. Results suggest that the pneumococcus phase varies between a virulent form with more capsular polysaccharide and less teichoic acid and an avirulent form with less capsular polysaccharide and more teichoic acid.

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Association of Intrastrain Phase Variation in Quantity of Capsular Polysaccharide and Teichoic Acid with the Virulence of Streptococcus pneumoniae

Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend on the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated whole-cell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD4+ T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD8+ T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD4+ T cells at the time of challenge.

/pdf/cd4-t-cells-mediate-antibody-independent-acquired-immunity-1v88r946sr.pdf

CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization

Fourteen new capsular types of Streptococcus suis (types 9 to 22) are described. All reference strains are morphologically and biochemically similar to types previously described. Reference strain types 9 to 13, 15, 16, and 22 were isolated from diseased pigs, whereas types 17 to 19 and 21 came from clinically healthy pigs; type 14 was isolated from a human case of meningitis, and type 20 was isolated from a diseased calf. The group T streptococcus of de Moor has been included in the typing system as type 15. Two-way cross-reactions between types 6 and 16 and a one-way cross-reaction between types 2 and 22 have been demonstrated. In addition, several cross-reactions probably not due to capsular material were detected among different types by using the coagglutination test. This test should not be used alone; weak or multiple positive reactions must be confirmed by the capsular reaction test or the capillary precipitation test.

Description of 14 new capsular types of Streptococcus suis.

The localization of pneumococcal capsular and cell wall antigens was examined by immunoelectron microscopy. C polysaccharide (C-Ps), a common component of all pneumococci, was uniformly distributed on both the inside and outside of the cell walls. The thickness of the C-Ps varied with the strain. Encapsulated strains were covered by varied amounts of capsular polysaccharide concealing the C-Ps of the bacteria so as to render it inaccessible to anti-C-Ps antibodies. In addition to C-Ps, protein antigens were demonstrable on the surface of nonencapsulated pneumococci. The proteins were not masked by the C-Ps layer. An extra layer on the cell walls was conspicuous on electron micrographs of both rough and encapsulated pneumococci. The nature of this extra layer has not been disclosed. F antigen, another common antigen of pneumococci, was uniformly distributed on the surface of the plasma membranes. During the course of the experimental work a reproducible method of gold labeling immunoglobulins was developed.

https://iai.asm.org/content/iai/56/8/1890.full.pdf

U B Skov Sørensen

Papers

Ultrastructural localization of capsules, cell wall polysaccharide, cell wall proteins, and F antigen in pneumococci.