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CPS polymers are anchored in the meningococcal outer membrane through a 1,2-diacylglycerol moiety, but the innate immunostimulatory activity of CPS is largely unexplored. Well-established human and murine macrophage cell lines and HEK\/TLR stably transfected cells were stimulated with CPS, purified from an endotoxin-deficient meningococcal serogroup B NMB-lpxA mutant. CPS induced inflammatory responses via TLR2- and TLR4-MD-2. Meningococcal CPS induced a dose-dependent release of cytokines (TNF-\u03b1, IL-6, IL-8, and CXCL10) and NO from human and murine macrophages, respectively. CPS induced IL-8 release from HEK cells stably transfected with TLR2\/6, TLR2, TLR2\/CD14, and TLR4\/MD-2\/CD14 but not HEK cells alone. mAb to TLR2 but not an isotype control antibody blocked CPS-induced IL-8 release from HEK-TLR2\/6-transfected cells. A significant reduction in TNF-\u03b1 and IL-8 release was seen when THP-1- and HEK-TLR4\/MD-2-CD14- but not HEK-TLR2- or HEK-TLR2\/6-transfected cells were stimulated with CPS in the presence of Eritoran (E5564), a lipid A antagonist that binds to MD-2, and a similar reduction in NO and TNF-\u03b1 release was also seen in RAW 264.7 cells in the presence of Eritoran. CD14 and LBP enhanced CPS bioactivity, and NF-\u03baB was, as anticipated, the major signaling pathway. Thus, these data suggest that innate immune recognition of meningococcal CPS by macrophages can occur via TLR2- and TLR4-MD-2 pathways.<\/jats:p>","DOI":"10.1189\/jlb.0610369","type":"journal-article","created":{"date-parts":[[2010,12,30]],"date-time":"2010-12-30T10:10:16Z","timestamp":1293703816000},"page":"469-480","source":"Crossref","is-referenced-by-count":62,"title":["<i>Neisseria meningitidis<\/i> capsular polysaccharides induce inflammatory responses via TLR2 and TLR4-MD-2"],"prefix":"10.1093","volume":"89","author":[{"given":"Susu M","family":"Zughaier","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,29]]},"reference":[{"key":"2023020612001310700_B1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1128\/IAI.72.1.371-380.2004","article-title":"Neisseria meningitidis lipooligosaccharide structure-dependent activation of the macrophage CD14\/Toll-like receptor 4 pathway","volume":"72","author":"Zughaier","year":"2004","journal-title":"Infect. 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