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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\u2010containing family of proteins (NLR) that functions as an intracellular receptor for a minimal motif present in all bacterial peptidoglycans. Furthermore, we have shown that this NLR is essential for glial responses to gram\u2010negative pathogens and <jats:italic>in vivo<\/jats:italic> CNS inflammation elicited by these organisms. In the present study, we have established that intact <jats:italic>Streptococcus pneumoniae<\/jats:italic>, the major causative agent for gram\u2010positive bacterial meningitis in adults, is a potent stimulus for the activation of the pivotal inflammatory transcription factor NF\u2010kB and production of inflammatory cytokines in primary murine microglia and astrocytes. We demonstrate that NOD2 is essential for the maximal responses of these cells to intact <jats:italic>S. pneumoniae<\/jats:italic> but not cellular lysates. Finally, we have shown that this cytosolic pattern recognition receptor is required for the elevated inflammatory mediator levels, astrogliosis, and demyelination, following <jats:italic>in vivo<\/jats:italic> administration of this gram\u2010positive CNS pathogen. As such, we suggest that NOD2 plays a critical role in the establishment of the lethal inflammation associated with streptococcal meningitis. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20968","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T15:48:00Z","timestamp":1264002480000},"page":"839-847","source":"Crossref","is-referenced-by-count":71,"title":["NOD2 mediates inflammatory responses of primary murine glia to <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1002","volume":"58","author":[{"given":"Xinjie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinita S.","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy 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