title: Interleukin-8 induction by Burkholderia pseudomallei can occur without Toll-like receptor signaling but requires a functional type III secretion system.
abstract: Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease that can result in asymptomatic, chronic, or acute illness. In acute melioidosis, high levels of proinflammatory cytokines and chemokines are found in organs and blood, and neutrophils play a key role in controlling the infection. We showed that B. pseudomallei activates NF-kappaB via Toll-like receptor (TLR) 2, TLR4, and TLR5 but can also activate NF-kappaB and induce interleukin (IL)-8 without involving TLRs. TLR-independent activation depends on a functional Bsa type III secretion system (T3SS) and requires internalization. The mitogen-activated protein kinase (MAPK) inhibitors for p38 and c-Jun N-terminal kinase (JNK) severely impaired IL-8 induction by B. pseudomallei and reduced bacterial internalization. Furthermore, the T3SS mutant induced less JNK phosphorylation than did wild-type bacteria. Thus, in cells with no or low expression of TLRs, such as mucosal epithelial cells, B. pseudomallei can induce IL-8 via NF-kappaB and MAPK pathways, aided by Bsa T3SS.
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Chung-Shii
authors.initials: CS
authors.lastname: Hii
authors.forename: Guang Wen
authors.initials: GW
authors.lastname: Sun
authors.forename: Jason Wee Kang
authors.initials: JW
authors.lastname: Goh
authors.forename: Jinhua
authors.initials: J
authors.lastname: Lu
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
authors.forename: Yunn-Hwen
authors.initials: YH
authors.lastname: Gan
mesh_terms: D001426:Bacterial Proteins / Q000502:physiology*; D016957:Burkholderia pseudomallei / Q000276:immunology*; D002460:Cell Line; D003593:Cytoplasm / Q000382:microbiology / Q000648:ultrastructure; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D026901:Membrane Transport Proteins / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D051193:Toll-Like Receptors; D037521:Virulence Factors