title: Recognition of Staphylococcus aureus-derived peptidoglycan (PGN) but not intact bacteria is mediated by CD14 in microglia.
abstract: Recognition of Staphylococcus aureus and its cell-wall component peptidoglycan (PGN) by microglia is mediated, in part, by Toll-like receptor 2 (TLR2). However, the pattern recognition receptor (PRR) CD14 can also bind PGN and enhance TLR2-mediated signaling in macrophages, suggesting a similar phenomenon might occur in microglia. To assess the functional significance of CD14 on microglial activation, we evaluated the responses of primary microglia isolated from CD14 knockout (KO) and wild type (WT) mice. PGN-dependent microglial activation was partially CD14-dependent as demonstrated by the attenuated expression of TNF-alpha, macrophage inflammatory protein-2 (MIP-2/CXCL2), and the soluble PRR pentraxin-3 in CD14 KO microglia compared to WT cells. In contrast, microglial responses to intact S. aureus occurred primarily via a CD14-independent manner. Collectively, these findings reveal the complex nature of gram-positive bacterial recognition by microglia, which occurs, in part, via CD14.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham St., Slot 846, Little Rock, AR 72205, USA.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Esen
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002097:C-Reactive Protein; D054426:Chemokine CXCL2; D018925:Chemokines; D018950:Lipopolysaccharide Receptors; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C404915:Cxcl2 protein, mouse; C507780:Myd88 protein, mouse