| First Author | Echchannaoui H | Year | 2005 |
| Journal | J Leukoc Biol | Volume | 78 |
| Issue | 3 | Pages | 705-15 |
| PubMed ID | 15941778 | Mgi Jnum | J:100487 |
| Mgi Id | MGI:3588621 | Doi | 10.1189/jlb.0205063 |
| Citation | Echchannaoui H, et al. (2005) CD14 deficiency leads to increased MIP-2 production, CXCR2 expression, neutrophil transmigration, and early death in pneumococcal infection. J Leukoc Biol 78(3):705-15 |
| abstractText | CD14 is a myeloid receptor for bacterial cell membrane/wall components, for which we previously showed a strong induction in cerebrospinal fluid (CSF) during meningitis. Here, we studied CD14 function in murine Streptococcus pneumoniae meningitis by using wild-type (WT), CD14(-/-) mice, and WT mice pretreated with neutralizing anti-CD14 antibodies. Early polymorphonuclear leukocytes (PMN) immigration was more pronounced in CSF of CD14(-/-) than of WT mice. This was not a result of altered adherence molecule expression in blood and CSF PMN or brain endothelial cells. Macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine levels were similar in CSF in both strains, but MIP-2 was higher in infected brain and in brain-derived endothelial cells infected in vitro in CD14(-/-) than in WT mice. CD14(-/-) PMN demonstrated increased expression of CXC chemokine receptor 2 (CXCR2) after infection and stronger in vitro chemotaxis than WT PMN toward CSF from WT or CD14(-/-) mice and toward MIP-2. Excess PMN migration in CD14(-/-) mice did not result in improved bacterial clearing but in increased tumor necrosis factor in CSF, higher disease severity, and earlier death. Pretreatment with anti-CXCR2 reduced PMN infiltration into CSF and brain MIP-2 production and abolished earlier mortality in CD14(-/-) mice. In conclusion, CD14 plays a protective role in pneumococcal meningitis by slowing PMN migration via MIP-2 and CXCR2 modulation. |
