Insights Into the Effects of Mucosal Epithelial and Innate Immune Dysfunction in Older People on Host Interactions With Streptococcus pneumoniae

Abstract

In humans, nasopharyngeal carriage of Streptococcus pneumoniae is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together, these kill over 500,000 people over the age of 70 years worldwide every year. Pneumococcal conjugate vaccines have been largely successful in reducing IPD in young children and have had considerable indirect impact in protection of older people in industrialized country settings (herd immunity). However, serotype replacement continues to threaten vulnerable populations, particularly older people in whom direct vaccine efficacy is reduced. The early control of pneumococcal colonization at the mucosal surface is mediated through a complex array of epithelial and innate immune cell interactions. Older people often display a state of chronic inflammation, which is associated with an increased mortality risk and has been termed ‘Inflammageing’. In this review, we discuss the contribution of an altered microbiome, the impact of inflammageing on human epithelial and innate immunity to S. pneumoniae, and how the resulting dysregulation may affect the outcome of pneumococcal infection in older individuals. We describe the impact of the pneumococcal vaccine and highlight potential research approaches which may improve our understanding of respiratory mucosal immunity during pneumococcal colonization in older individuals.

N , N -Dimethyldithiocarbamate Elicits Pneumococcal Hypersensitivity to Copper and Macrophage-Mediated Clearance

“…As a result of autolyzed bacterial contents being in the blood, phagocytosis of intact bacteria by peripheral blood mononuclear cells is impaired ( 20 – 22 ). Accordingly, there is also a substantial body of evidence to suggest that the pneumococcus may be more prone to infecting the elderly due to a decline in innate immune system activity with age ( 13 , 23 , 24 ).…”

The Impact of Immune System Aging on Infectious Diseases

“…In these patients, both antibody opsonic activities for all tested pneumococcal serotypes and phagocytic killing of pneumococci by neutrophils were significantly impaired [191]. The increased senescence markers, such as IL-1α/β, TNF-α, IL-6, and C-X-C motif chemokine ligand (CXCL)1, and cellular senescence facilitate bacterial adhesion to cells in the lungs [192], and may compromise upper respiratory mucosal immunity [193]. In addition, CD27+IgM+ B cells, which provide protection from Streptococcus pneumoniae and show age-related changes, may account for a reduced response to bacterial antigens [194].…”

SPD_0090 Negatively Contributes to Virulence of Streptococcus pneumoniae

“…An estimated 14.5 million children are infected with S. pneumoniae each year, two-thirds of which occur in Asia or Africa. Therefore, the World Health Organization considers S. pneumoniae to be a priority bacterium requiring urgent development of novel antibiotics or anti-infective strategies ( Kadioglu et al, 2008 ; Weight et al, 2021 ).…”