{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:41:45Z","timestamp":1791200505451,"version":"4.2.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,9,19]],"date-time":"2008-09-19T00:00:00Z","timestamp":1221782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>While glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation that resident central nervous system (CNS) cells initiate and\/or augment inflammation following trauma or infection. We have recently demonstrated that microglia and astrocytes constitutively express nucleotide\u2010binding oligomerization domain\u20102 (NOD2), a member of the novel nucleotide\u2010binding domain leucine\u2010rich repeat region containing a family of proteins (NLR) that functions as an intracellular receptor for a minimal motif present in all bacterial peptidoglycans. In this study, we have confirmed the functional nature of NOD2 expression in astrocytes and microglia and begun to determine the relative contribution that this NLR makes in inflammatory CNS responses to clinically relevant bacterial pathogens. We demonstrate the increased association of NOD2 with its downstream effector molecule, Rip2 kinase, in primary cultures of murine microglia and astrocytes following exposure to bacterial antigens. We show that this cytosolic receptor underlies the ability of muramyl dipeptide to augment the production of inflammatory cytokines by glia following exposure to specific ligands for disparate Toll\u2010like receptor homologues. In addition, we demonstrate that NOD2 is an important component in the <jats:italic>in vitro<\/jats:italic> inflammatory responses of resident glia to <jats:italic>N. meningitidis<\/jats:italic> and <jats:italic>B. burgdorferi<\/jats:italic> antigens. Finally, we have established that NOD2 is required, at least in part, for the astrogliosis, demyelination, behavioral changes, and elevated inflammatory cytokine levels observed following <jats:italic>in vivo<\/jats:italic> infection with these pathogens. As such, we have identified NOD2 as an important component in the generation of damaging CNS inflammation following bacterial infection. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20770","type":"journal-article","created":{"date-parts":[[2008,9,20]],"date-time":"2008-09-20T02:10:14Z","timestamp":1221876614000},"page":"414-423","source":"Crossref","is-referenced-by-count":82,"title":["NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens"],"prefix":"10.1002","volume":"57","author":[{"given":"Vinita S.","family":"Chauhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"David G.","family":"Sterka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha R.","family":"Furr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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