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: Invasion and Inflammation

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  • Authors: Allister J. Loughran1, Carlos J. Orihuela2, Elaine I. Tuomanen3
  • Editors: Vincent A. Fischetti4, Richard P. Novick5, Joseph J. Ferretti6, Daniel A. Portnoy7, Miriam Braunstein8, Julian I. Rood9
    Affiliations: 1: Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105; 2: Department of Microbiology, The University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294; 3: Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105; 4: The Rockefeller University, New York, NY; 5: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 6: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 7: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 8: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 9: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0004-2018
  • Received 30 April 2018 Accepted 19 October 2018 Published 15 March 2019
  • Elaine I. Tuomanen, [email protected]
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  • Abstract:

    Streptococcus pneumoniae (the pneumoccus) is the leading cause of otitis media, community-acquired pneumonia, and bacterial meningitis. The success of the pneumococcus stems from its ability to persist in the population as a commensal and avoid killing by immune system. This chapter first reviews the molecular mechanisms that allow the pneumococcus to colonize and spread from one anatomical site to the next. Then, it discusses the mechanisms of inflammation and cytotoxicity during emerging and classical pneumococcal infections.

  • Citation: Loughran A, Orihuela C, Tuomanen E. 2019. : Invasion and Inflammation. Microbiol Spectrum 7(2):GPP3-0004-2018. doi:10.1128/microbiolspec.GPP3-0004-2018.


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Streptococcus pneumoniae (the pneumoccus) is the leading cause of otitis media, community-acquired pneumonia, and bacterial meningitis. The success of the pneumococcus stems from its ability to persist in the population as a commensal and avoid killing by immune system. This chapter first reviews the molecular mechanisms that allow the pneumococcus to colonize and spread from one anatomical site to the next. Then, it discusses the mechanisms of inflammation and cytotoxicity during emerging and classical pneumococcal infections.

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Image of FIGURE 1

Immunohistochemical and schematic depiction of the choline biology of the pneumococcal surface. Immunogold labeling of pneumococci with TEPC-15 antibody recognizing free choline and antiautolysin antibody. These two images contrast free (A) versus CBP-bound (B) choline. Schematic view of the capsule (blue), cell wall (green), and membrane (red). The teichoic and lipoteichoic acids are indicated as dark blue lines bearing choline (circles). A proportion of these are capped by choline-binding proteins. Courtesy of K.G. Murti, St. Jude Electron Microscopy Core Facility.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0004-2018
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Image of FIGURE 2

Schematic depiction of the spread and progression of infection. Carriage of the pneumococcus occurs in the nasopharynx and is usually asymptomatic in healthy individuals. The bacteria are spread by aerosol from the nasopharynx of carriers. The pneumococcus can spread from the nasopharynx to a number of different tissues. In children the bacteria usually causes otitis media. Invasive diseases generally start in the lungs and spread to the blood, with the most serious complication being meningitis. The switch from asymptomatic colonization to invasive disease in healthy individuals usually occurs when there is a disruption in the innate immune defenses. (This figure contains some artwork produced by Servier Medical Art [http://smart.servier.com/] under Creative Commons license 3.0).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0004-2018
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Image of FIGURE 3

Schematic representation of the pneumococcus hijacking the pIgR/IgA system to cross the mucosal epithelia into the blood. Mucosal epithelial cells transport IgA (black) from the basolateral to the apical surface using the receptor pIgR (green). This receptor is then endocytosed and recycled back to the basolateral surface to transport more IgA. To protect itself from IgA, the pneumococcus produces the protease sIgA1 (yellow), which cleaves the host IgA into Fab fragments. The choline-binding protein, CbpA (red), binds to the empty pIgR and shuttles the pneumococcus from the apical side to the basolateral side of the epithelial cells. (This figure contains some artwork produced by Servier Medical Art [http://smart.servier.com/] under Creative Commons license 3.0).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0004-2018
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Image of FIGURE 4

Structure of the pneumococcal cell wall and its relationship to inflammation. Penicillin induces cell wall degradation by the autolysin releasing cell wall fragments such as lipoteichoic acid, glycan polymers with and without teichoic acid, and small stem peptides. All teichoicated species contain ChoP, a key component increasing inflammatory activity. All of these components interact with a variety of human cells, which in turn produce inflammatory mediators. Particularly important in this response is the platelet activating factor (PAFr). These mediators combine to produce the symptomatology of pneumococcal infection, including changes in blood flow, fluid balance in the tissue, and leukocytosis. Glc, glucose; TDH, trideoxyhexose; NAcGaln, -acetylgalctosamine; Galn, galactosamine; -Ala, -alanine; -Glu, -glucose; -Lys, -lysine; TNF, tumor necrosis factor; NO, nitric oxide; PGE2, prostaglandin E2; IC pressure, intracranial pressure; MIPS, macrophage inflammatory protein.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0004-2018
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Image of FIGURE 5

Domain structure of pneumolysin. Pneumolysin has three functionally separate domains: one activating complement, one causing hemolysis, and the other binding to cholesterol. Site-specific mutations alter these properties individually ( 191 , 192 ).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0004-2018
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