Dura:Gnegative LPS/ CNS immune response

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J Neurochem. 2001 Nov;79(3):648-57.

Circulating cell wall components derived from gram-negative, not gram-

positive, bacteria cause a profound induction of the gene-encoding

Toll-like receptor 2 in the CNS.

Laflamme N, Soucy G, Rivest S.

Laboratory of Molecular Endocrinology, CHUL Research Center and

Department of Anatomy and Physiology, Laval University, Quebec,

Canada.

The recent characterization of human homologs of Toll may be the

missing link for the transduction events leading to nuclear factor-

kappaB (NF-kappaB) activity and proinflammatory gene transcription

during innate immune response. Mammalian cells may express as many as

10 distinct Toll-like receptors (TLRs), although TLR2 is a key

receptor for recognizing cell wall components of Gram-positive

bacteria. The present study investigated the effects of circulating

bacterial cell wall components on the expression of the gene-encoding

TLR2 across the mouse brain.

Surprisingly, while Gram-negative components caused a robust

increase in TLR2 transcription within the cerebral tissue,

peptidoglycan (PGN) and lipoteichoic acid (LTA), either alone or

combined, failed to modulate the receptor transcript. Indeed, the

mRNA levels for TLR2 in the choroid plexus and few other regions of

the brain remained similar between vehicle-, LTA-, PGN-, and LTA/PGN-

administered mice at all the times evaluated (i.e. 30 min to 24 h

post-intraperitoneal injection).

This contrasts with the profound de novo expression of TLR2 following

a single systemic injection of the lipopolysaccharide (LPS). The

signal was first detected in regions devoid of blood-brain barrier

and few blood vessels and microcapillaries. A second wave of TLR2

expression was also detected from these structures to their

surrounding parenchymal cells that stained for a microglial marker

iba1. The rapid induction of IkappaBalpha (index of NF-kappaB

activity) and up-regulation of the adaptor protein MyD88 suggest that

LPS-induced TLR2 transcription may be dependent on the NF-kappaB

pathway.

These data provide the evidence that TLR2 is not only present in the

brain, but its encoding gene is regulated by cell wall components

derived from Gram-negative, not Gram-positive, bacteria. The robust

wave of TLR2-expressing microglial cells may have a determinant

impact on the innate immune response that occurs in the brain during

systemic infection by Gram-negative, not Gram-positive, bacteria.

PMID: 11701768 [PubMed - indexed for MEDLINE]