Host response to Neisseria meningitidis lacking lipopolysaccharides.
Plasma levels of lipopolysaccharides are closely associated with disease manifestations and outcomes in meningococcal infections. The knockout mutant lpxA-Neisseria meningitidis completely lacking lipopolysaccharides has made it possible to study the contribution of nonlipopolysaccharide molecules in the bacterial cell wall to the host's response. The lpxA-N. meningitidis requires 10- to 100-fold higher concentrations of bacteria to elicit the same level of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and -6) as the wild type parent strain. It activates human mononuclear peripheral blood cells through CD14 and Toll-like receptor-2 receptor complex whereas the wild type strain activates these cells through the CD14-Toll-like receptor-4-MD2 pathway. Dendritic cells are hardly activated by the lpxA-N. meningitidis. It is as efficient as the wild type strain in activating complement. The lpxA-N. meningitidis expresses pili but does not adhere or invade mucosal cells normally. The defensin-mediated adhesion of lpxA-N. meningitidis to the respiratory epithelial cells is severely reduced as compared with the wild-type strain.
Brandtzaeg
Petter
P
Department of Pediatrics, Ullevål University Hospital, University of Oslo, N-0407 Oslo, Norway. petter.brandtzag@ioks.uio.no
D001422:Bacterial Adhesion; D023082:Defensins / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity*; D008562:Membrane Glycoproteins / Q000502:physiology; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D023082:Defensins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors