Thein vivoandin vitroRoles of Epithelial Pattern Recognition Receptors in Pneumococcal Infections

Abstract

Streptococcus pneumoniae, also called pneumococcus, is a major cause of infectious disease in human. Pneumococcus resides in the nasopharynx as an upper respiratory commensal, and most of pneumococcal colonizations are asymptomatic in immunocompetent individuals. When nasopharyngeal mucosal homeostasis is disrupted, pneumococcus migrates into middle ear and lower respiratory tract and causes detrimental colonization. In this regard, the epithelial cells of middle ear and lung act as first line of defense against pneumococcus to prevent invasive pneumococcal diseases. Respiratory epithelial cells express various cell-surface and intra-cellular receptors sensing microbial pathogens and respond to sensed pathogens by triggering intra-cellular signaling pathways and inducing pathogen-specific innate immune responses. Various epithelial cell-surface and intra-cellular receptors, such as Toll-like receptors (TLRs), Nod-like receptors (NLRs), intracellular DNA sensing receptors, and scavenger receptors (SRs), participate in sensing of pneumococcus, and the activation of these receptors by pneumococcal components induces anti-pneumococcal innate immune responses including epithelial apoptosis and inflammatory cytokine/chemokine expressions. Epithelial sensing of pneumococcus is a critical step for setting an early defense against pneumococcal infection, and also is required to recruit and activate innate immune cells and trigger adaptive immunity.

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

“…These findings suggested that recognition of PspK, likely the R3 domain, by annexin A2 was critical for developing or activating anti-pneumococcal immune responses and subsequent clearance of intra-epithelial pneumococci in epithelial cells. Annexin A2 activation by bacterial antigens is known to modulate Toll-like receptor (TLR) and kinase signaling pathways, which are also known to be activated by pneumococcus in epithelial cells., 35,36,49,50 Thus, further studies of PspK-annexin A2-mediated intracellular signaling pathways are required to improve our understanding of the role of this interaction in the pathogenesis of pneumococcal infections in epithelial cells. Although the mechanisms and downstream signaling pathways involved in this interaction were not fully elucidated in this study, our results provided the first evidence of a direct interaction between gram-positive bacteria and annexin A2 during the process of bacterial adherence and invasion.…”

PAI-1 inhibits development of chronic otitis media and tympanosclerosis in a mouse model of otitis media

“…Although the etiology of tympanosclerosis is not clearly understood yet, the prolonged inflammation or delayed resolution of middle ear inflammation is thought to significantly contribute to the pathophysiology of tympanosclerosis. We previously reported that Streptococcus pneumoniae, another common bacterial pathogen in OM, up-regulates PAI-1, and PAI-1 plays a critical role in protecting against S. pneumoniae-induced acute lung injury in severe pneumococcal pneumonia [19,20]. These findings suggest a possible role of PAI-1 in regulating S. pneumoniae-induced OM.…”

TBX21 participates in innate immune response by regulating Toll‐like receptor 2 expression in Streptococcus pneumoniae infections

“…These data suggest that pneumococcus may regulate TLR2 expression and subsequent innate immune responses through the regulation of TBX21 expression. As TLR4 and TLR9, along with TLR2, act as critical receptors for pneumococcus (Shin et al ., ), the effects of D39 and siTBX21 on TLR4 and TLR9 expression were also determined. As shown in Fig.…”