title: Pathogenic Triad in Bacterial Meningitis: Pathogen Invasion, NF-κB Activation, and Leukocyte Transmigration that Occur at the Blood-Brain Barrier.
abstract: Bacterial meningitis remains the leading cause of disabilities worldwide. This life-threatening disease has a high mortality rate despite the availability of antibiotics and improved critical care. The interactions between bacterial surface components and host defense systems that initiate bacterial meningitis have been studied in molecular and cellular detail over the past several decades. Bacterial meningitis commonly exhibits triad hallmark features (THFs): pathogen penetration, nuclear factor-kappaB (NF-κB) activation in coordination with type 1 interferon (IFN) signaling and leukocyte transmigration that occur at the blood-brain barrier (BBB), which consists mainly of brain microvascular endothelial cells (BMEC). This review outlines the progression of these early inter-correlated events contributing to the central nervous system (CNS) inflammation and injury during the pathogenesis of bacterial meningitis. A better understanding of these issues is not only imperative to elucidating the pathogenic mechanism of bacterial meningitis, but may also provide the in-depth insight into the development of novel therapeutic interventions against this disease.
authors.affiliation: Department of Children's Medical Laboratory Diagnosis Center, Qilu Children's Hospital of Shandong UniversityJinan, China; Children's Hospital Los Angeles, Keck School of Medicine, University of Southern CaliforniaLos Angeles, CA, USA.
authors.forename: Shifu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Guangzhou Medical University Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Children's Medical Laboratory Diagnosis Center, Qilu Children's Hospital of Shandong University Jinan, China.
authors.forename: Zhongtao
authors.initials: Z
authors.lastname: Gai
authors.affiliation: Department of Children's Medical Laboratory Diagnosis Center, Qilu Children's Hospital of Shandong University Jinan, China.
authors.forename: Lehai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Ambrose
authors.initials: A
authors.lastname: Jong
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health and Tropical Medicine, Southern Medical University Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
keywords: NF-κB activation; bacterial meningitis; blood-brain barrier; leukocyte transmigration; pathogen invasion; pathogenic triad