Host response to Neisseria meningitidis lacking lipopolysaccharides

Abstract

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-α, interleukin-1β 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.

• complement
• defensin
• interferon-γ
• lipopolysaccharide
• meningitis
• Neisseria meningitidis
• pilus
• sepsis
• Toll-like receptors-2 and -4
• tumor necrosis factor-α