Inflammasomes in Pneumococcal Infection: Innate Immune Sensing and Bacterial Evasion Strategies

Abstract

Streptococcus pneumoniae frequently colonizes the upper respiratory tract of healthy individuals, but also commonly causes severe invasive infections such as community-acquired pneumonia and meningitis. One of the key virulence factors of pneumococci is the pore-forming toxin pneumolysin which stimulates cell death and is involved in the evasion of some defense mechanisms. The immune system, however, employs different inflammasomes to sense pneumolysin-induced pore formation, cellular membrane damage, and/or subsequent leakage of bacterial nucleic acid into the host cell cytosol. Canonical inflammasomes are cytosolic multiprotein complexes consisting of a receptor molecule such as NLRP3 or AIM2, the adapter ASC, and caspase-1. NLRP3 and AIM2 inflammasomes mediate cell death and production of important IL-1 family cytokines to recruit leukocytes and defend against S. pneumoniae. Here, we review recent evidence that highlights inflammasomes as critical sensors of S. pneumoniae-induced cellular perturbations, summarize their role in pneumococcal infections, and discuss potential evasion strategies of some emerging pneumococcal strains.

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

“…Below we further discuss virulence factors of particular interest: Polysaccharide capsule: S. pneumoniae’s extracellular polysaccharide capsule, the most important virulence factor ( 55 ), helps to initiate infection by allowing the bacterium to adhere to host cells and cause inflammation, while also providing protection from the host’s immune system ( 54 , 55 ). The capsule inhibits phagocytosis by innate immune cells, prevents the recognition of the bacterium by host receptors and complement factors, and also avoids neutrophil traps ( 17 , 27 , 55 , 56 , 71 , 123 ). Many serotypes of S. pneumoniae are characterized by the polysaccharides that are on the outer coat of the capsule, and they are all pathogenic in their own unique manner—some more harmful than others ( 20 , 56 ).…”

“…The capsule inhibits phagocytosis by innate immune cells, prevents the recognition of the bacterium by host receptors and complement factors, and also avoids neutrophil traps ( 17 , 27 , 55 , 56 , 71 , 123 ). Many serotypes of S. pneumoniae are characterized by the polysaccharides that are on the outer coat of the capsule, and they are all pathogenic in their own unique manner—some more harmful than others ( 20 , 56 ). For example, serotype 1 has been found in invasive infections which have lower fatalities, whereas serotype 3 is associated with colonization of the nasopharynx and serious infections which can lead to fatalities ( 39 , 42 , 56 , 124 , 125 ).…”

Proteomic Investigation Uncovers Potential Targets and Target Sites of Pneumococcal Serine-Threonine Kinase StkP and Phosphatase PhpP

“…In addition to that the emergence of antimicrobial resistance in bacterial infections has become a major public health concern worldwide. The pneumococcus overcomes not only the stress and starvation conditions of the ever-dynamic settings of bacterial habitats, but also the host defense mechanisms and antibiotic treatments (Koppe et al, 2012;Saleh et al, 2013;Kohler et al, 2016;Rabes et al, 2016). Additionally, S. pneumoniae is increasingly resistant to the most common clinically used drugs such as beta-lactam antibiotics and macrolides (Schulz and Hammerschmidt, 2013;Gladstone et al, 2019;Peyrani et al, 2019).…”

Congenitally impaired pattern-recognition receptors in pathogenesis of pediatric invasive and recurrent pneumococcal infection

“…В недавнем обзоре A. Rabes и соавт. показана критически важная роль канонических инфламмасом с участием паттерн-распознающих рецепторов NLRP3/AIM2 и адаптера ASC в механизмах противо пневмококковой защиты [31].…”