Streptococcus pneumoniae's Virulence and Host Immunity: Aging, Diagnostics, and Prevention

Abstract

Streptococcus pneumoniae is an infectious pathogen responsible for millions of deaths worldwide. Diseases caused by this bacterium are classified as pneumococcal diseases. This pathogen colonizes the nasopharynx of its host asymptomatically, but overtime can migrate to sterile tissues and organs and cause infections. Pneumonia is currently the most common pneumococcal disease. Pneumococcal pneumonia is a global health concern and vastly affects children under the age of five as well as the elderly and individuals with pre-existing health conditions. S. pneumoniae has a large selection of virulence factors that promote adherence, invasion of host tissues, and allows it to escape host immune defenses. A clear understanding of S. pneumoniae's virulence factors, host immune responses, and examining the current techniques available for diagnosis, treatment, and disease prevention will allow for better regulation of the pathogen and its diseases. In terms of disease prevention, other considerations must include the effects of age on responses to vaccines and vaccine efficacy. Ongoing work aims to improve on current vaccination paradigms by including the use of serotype-independent vaccines, such as protein and whole cell vaccines. Extending our knowledge of the biology of, and associated host immune response to S. pneumoniae is paramount for our improvement of pneumococcal disease diagnosis, treatment, and improvement of patient outlook.

Keywords: immunology; pathogenesis; pneumococcal; respiratory; virulence.

Figure 1

Global distribution of lower respiratory infections by sex. Highlighted in this figure is the distribution of the disability adjusted life year (DALY) per 100,000 (2016) for four major lower respiratory infections worldwide by sex. Data obtained from Institute for Health Metrics and Evaluation (7).

Figure 2

Global distribution of lower respiratory infections with age. This figure shows the age-dependent disease burden to lower respiratory infections especially pneumococcal pneumonia based on the disability adjusted life year (DALY) data from 2016. Data obtained from Institute for Health Metrics and Evaluation (7).

Figure 3

Schematic cross section of Streptococcus pneumoniae cell wall. The bacterial cell wall composes of teichoic acids, a thick peptidoglycan layer, and a phospholipid bilayer.

Figure 4

Virulence factors of Streptococcus pneumoniae. There are a variety of proteins and toxins that are expressed by S. pneumoniae that drive its pathogenesis. The major virulence factors are highlighted in the figure. Abbreviations: PsaA, pneumococcal surface adhesin A; PspA, pneumococcal surface protein A; PspC, pneumococcal surface protein C; PiaA, pneumococcal iron acquisition A; PiuA, pneumococcal iron uptake A; PitA, pneumococcal iron transporter.

Figure 5

Worldwide disability adjusted life year (DALY) of pneumococcal pneumonia. Global distribution of pneumococcal pneumonia on a log10 scale of the 2016 DALY per 100,000 pneumococcal pneumonia data obtained from Institute for Health Metrics and Evaluation (7).

Figure 6

Global distribution of lower respiratory infections over time. This figure depicts how the burden for four major lower respiratory infections changes over time in response to the introduction of antibiotic treatments and vaccine implementation. Disability adjusted life year (DALY) data obtained from Institute for Health Metrics and Evaluation (7).

Figure 7

Host surface and intracellular receptors necessary for immune response to Streptococcus pneumoniae. Highlighted in this figure are the major pathogen recognition receptors necessary for binding to pneumococcal ligands and eliciting an immune response. Upon binding to the ligands, receptors and signaling pathways are activated, which leads to the overall production of inflammatory cytokines and recruitment of immune cells. There are 10 toll-like receptors (TLRs) that have been discovered in humans—TLRs involved in pneumococcal disease are depicted in the figure.

Figure 8

Streptococcus pneumoniae’s interaction with host epithelial cells. Two types of epithelial cells are depicted: goblet cells and ciliated epithelial cells. The cilia on the epithelial cells together with the mucus produced by goblet cells clear the pathogen via mucociliary clearance. Epithelial cells can also secrete antimicrobial peptides that directly kill S. pneumoniae or produce cytokines, which leads to a state of inflammation and the recruitment of immune cells.

Figure 9

Toll-like receptors (TLRs) assist in the activation of adaptive immune cells. In this figure, TLR2 recognizes the Streptococcus pneumoniae’s lipoproteins. Upon activation, TLR2 secretes cytokines and co-stimulatory molecules. These co-stimulatory molecules are essential for co-stimulation and activation of T cells. The T cell is presented an antigen with major histocompatibility complex (MHC)II and antigen-presenting cell. The recognition of the antigen–MHCII complex and the co-stimulatory molecules activates the T cell and leads downstream to differentiation into Th1 and Th2 cells, that can release various cytokines such as interferon-gamma (IFN)-γ and interleukin (IL)-4.