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Pathog Dis. 2017 Apr 1;75(3). doi: 10.1093/femspd/ftx030.

Innate immune response to lipooligosaccharide: pivotal regulator of the pathobiology of invasive Neisseria meningitidis infections.

Author information

1
Center for Immunochemistry, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
2
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
3
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA.
4
University of Maryland, Department of Cell Biology and Molecular Genetics, College Park, MD 20742 USA.

Abstract

Infections due to Neisseria meningitidis afflict more than one million people worldwide annually and cause death or disability in many survivors. The clinical course of invasive infections has been well studied, but our understanding of the cause of differences in patient outcomes has been limited because these are dependent on multiple factors including the response of the host, characteristics of the bacteria and interactions between the host and the bacteria. The meningococcus is a highly inflammatory organism, and the lipooligosaccharide (LOS) on the outer membrane is the most potent inflammatory molecule it expresses due to the interactions of the lipid A moiety of LOS with receptors of the innate immune system. We previously reported that increased phosphorylation of hexaacylated neisserial lipid A is correlated with greater inflammatory potential. Here we postulate that variability in lipid A phosphorylation can tip the balance of innate immune responses towards homeostatic tolerance or proinflammatory signaling that affects adaptive immune responses, causing disease with meningitis only, or septicemia with or without meningitis, respectively. Furthermore, we propose that studies of the relationship between bacterial virulence and gene expression should consider whether genetic variation could affect properties of biosynthetic enzymes resulting in LOS structural differences that alter disease pathobiology.

KEYWORDS:

Neisseria meningitidis; adaptive immunity; endotoxin tolerance; innate immunity; lipooligosaccharide; proinflammatory

PMID:
28423169
DOI:
10.1093/femspd/ftx030
[Indexed for MEDLINE]

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