title: Role of oxidative stress in the pathophysiology of pneumococcal meningitis.
abstract: Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting the pia mater, the arachnoid, and the subarachnoid spaces. Streptococcus pneumoniae crosses the blood-brain barrier (BBB) by both transcellular traversal and disruption of the intraepithelial tight junctions to allow intercellular traversal. During multiplication, pneumococci release their bacterial products, which are highly immunogenic and may lead to an increased inflammatory response in the host. Thus, these compounds are recognized by antigen-presenting cells through the binding of toll-like receptors. These receptors induce the activation of myeloid differentiation factor 88 (MyD88), which interacts with various protein kinases, including IL-1 receptor-associated kinase-4 (IRAK4), which is phosphorylated and dissociated from MyD88. These products also interact with tumor necrosis factor receptor-associated factor 6 dependent signaling pathway (TRAF6). This cascade provides a link to NF- κ B-inducing kinase, resulting in the nuclear translocation of NF- κ B leading to the production of cytokines, chemokines, and other proinflammatory molecules in response to bacterial stimuli. Consequently, polymorphonuclear cells are attracted from the bloodstream and then activated, releasing large amounts of NO(•), O2(•), and H2O2. This formation generates oxidative and nitrosative stress, subsequently, lipid peroxidation, mitochondrial damage, and BBB breakdown, which contributes to cell injury during pneumococcal meningitis.
authors.affiliation: Laboratório de Microbiologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. tba@unesc.net
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Generoso
authors.forename: Lutiana R
authors.initials: LR
authors.lastname: Simões
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Elias
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007962:Leukocytes / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology*; D018384:Oxidative Stress