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CD14 deficiency leads to increased MIP‐2 production, CXCR2 expression, neutrophil transmigration, and early death in pneumococcal infection
Author(s) -
Echchannaoui Hakim,
Frei Karl,
Letiembre Maryse,
Strieter Robert M.,
Adachi Yoshiyuki,
Landmann Regine
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0205063
Subject(s) - cxc chemokine receptors , biology , cd14 , chemokine , immunology , meningitis , tumor necrosis factor alpha , streptococcus pneumoniae , microbiology and biotechnology , chemokine receptor , inflammation , medicine , flow cytometry , psychiatry , antibiotics
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.