Premium
Contributions of Neisseria meningitidis LPS and non‐LPS to proinflammatory cytokine response
Author(s) -
Sprong Tom,
Stikkelbroeck Nike,
Ley Peter,
Steeghs Liana,
Alphen Loek,
Klein Nigel,
Netea Mihai G.,
Meer Jos W. M.,
Deuren Marcel
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.2.283
Subject(s) - neisseria meningitidis , lipopolysaccharide , cytokine , biology , microbiology and biotechnology , neisseriaceae , tumor necrosis factor alpha , proinflammatory cytokine , sepsis , pathogenesis , immunology , bacteria , antibiotics , inflammation , genetics
To determine the relative contribution of lipopolysaccharide (LPS) and non‐LPS components of Neisseria meningitidis to the pathogenesis of meningococcal sepsis, this study quantitatively compared cytokine induction by isolated LPS, wild‐type serogroup B meningococci (strain H44/76), and LPS‐deficient mutant meningococci (strain H44/76[pLAK33]). Stimulation of human peripheral‐blood mononuclear cells with wild‐type and LPS‐deficient meningococci showed that non‐LPS components of meningococci are responsible for a substantial part of tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β production and virtually all interferon (IFN)‐γ production. Based on tricine sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis of LPS in proteinase K‐treated lysates of N. meningitidis H44/76, a quantitative comparison was made between the cytokine‐inducing capacity of isolated and purified LPS and LPS‐containing meningococci. At concentrations of >10 7 bacteria/mL, intact bacteria were more potent cytokine inductors than equivalent amounts of isolated LPS, and cytokine induction by non‐LPS components was additive to that by LPS. Experiments with mice showed that non‐LPS components of meningococci were able to induce cytokine production and mortality. The principal conclusion is that non‐LPS parts of N. meningitidis may play a role in the pathogenesis of meningococcal sepsis by inducing substantial TNF‐α, IL‐1β, and IFN‐γ production.