The Roles of Transient Receptor Potential Vanilloid 1 and 4 in Pneumococcal Nasal Colonization and Subsequent Development of Invasive Disease

Abstract

Transient receptor potential (TRP) channels, neuronal stimulations widely known to be associated with thermal responses, pain induction, and osmoregulation, have been shown in recent studies to have underlying mechanisms associated with inflammatory responses. The role of TRP channels on inflammatory milieu during bacterial infections has been widely demonstrated. It may vary among types of channels/pathogens, however, and it is not known how TRP channels function during pneumococcal infections. Streptococcus pneumoniae can cause severe infections such as pneumonia, bacteremia, and meningitis, with systemic inflammatory responses. This study examines the role of TRP channels (TRPV1 and TRPV4) for pneumococcal nasal colonization and subsequent development of invasive pneumococcal disease in a mouse model. Both TRPV1 and TRPV4 channels were shown to be related to regulation of the development of pneumococcal diseases. In particular, the influx of neutrophils (polymorphonuclear cells) in the nasal cavity and the bactericidal activity were significantly suppressed among TRPV4 knockout mice. This may lead to severe pneumococcal pneumonia, resulting in dissemination of the bacteria to various organs and causing high mortality during influenza virus coinfection. Regulating host immune responses by TRP channels could be a novel strategy against pathogenic microorganisms causing strong local/systemic inflammation.

The in vitro and in vivo antibacterial activities of uniflorous honey from a medicinal plant, Scrophularia ningpoensis Hemsl., and characterization of its chemical profile with UPLC-MS/MS

“…Ferroptosis and oxidative phosphorylation, involving upregulation of L-glutamic acid (C00025) and fumaric acid (C00122), were related to oxidative stress and oxidative damage to bacteria (Baecker et al, 2021). Inflammatory mediator regulation of TRP channels, involving up-regulation of histamine (C00388) and 12-keto-tetrahydro-leukotriene B4 (C02165), could explain the potential anti-inflammatory activity of S. ningpoensis honey (Kono et al, 2021). Biofilm formation-Vibrio cholerae, involving down-regulation of glucose 6-phosphate (C00092), was related to the antibiofilm activity of S. ningpoensis honey.…”

Nucleic acid sensing Toll-like receptors 3 and 9 play complementary roles in the development of bacteremia after nasal colonization associated with influenza co-infection

“…To model pneumococcal occult bacteremia without pneumonia usually occurring in children, we introduced a virulent strain serotype 6A [ 28 ]. Furthermore, to avoid a direct influx of bacterial suspension to the lung, we inoculated the bacteria in the nose without anesthesia [ 28 , 31 ].…”

“…The limit of detection was 666 CFU/ml. For the observation study of the time course of the pneumococcal invasive infection, the mice were monitored every 12 h for 12 days after the pneumococcal infection, as previously reported [ 28 , 31 ]. If the mice were found to be severely sick (shivering, decreased motor activity), they were immediately euthanized and the blood was collected for confirmation of pneumococcus.…”

“…Neutrophil and macrophage cell counts were performed as previously described [ 28 , 31 ]. The nasal lavages were pelleted at 1,500 rpm for 2 min, and resuspended in 200 µ l PBS containing 1% bovine serum albumin (BSA).…”

“…All studies were conducted according to the guidelines outlined by the National Science Foundation Animal Welfare Requirements and the Wakayama Medical University Animal Care and Use Committee. The study was approved by the Institutional Animal Care and Use Committee at Wakayama Medical University (permission number [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42].…”