TY - JOUR
T1 - Recognition of Staphylococcus aureus-derived peptidoglycan (PGN) but not intact bacteria is mediated by CD14 in microglia
AU - Esen, Nilufer
AU - Kielian, Tammy
N1 - Funding Information:
The authors would like to thank Dr. Mason Freeman for generously providing the CD14 KO mice, Dr. Paul Drew for critical review of the manuscript, and Patrick Mayes for excellent technical assistance. This work was supported by the NIH National Institute of Mental Health (RO1 MH65297) to T.K. and the National Institute of Neurological Disorders and Stroke supported Core facility at UAMS (P30 NS047546).
PY - 2005/12/30
Y1 - 2005/12/30
N2 - 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-α, 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.
AB - 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-α, 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.
KW - CD14
KW - Central nervous system
KW - Lipopolysaccharide
KW - Microglia
KW - Pentraxin-3
KW - Peptidoglycan
KW - S. aureus
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U2 - 10.1016/j.jneuroim.2005.09.003
DO - 10.1016/j.jneuroim.2005.09.003
M3 - Article
C2 - 16229899
AN - SCOPUS:28444498105
SN - 0165-5728
VL - 170
SP - 93
EP - 104
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -