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CD14 is a key organizer of microglial responses to CNS infection and injury

Janova, H., Boettcher, C., Holtman, I. R., Regen, T., van Rossum, D., Goetz, A., Ernst, A-S., Fritsche, C., Gertig, U., Saiepour, N., Gronke, K., Wrzos, C., Ribes, S., Rolfes, S., Weinstein, J., Ehrenreich, H., Pukrop, T., Kopatz, J., Stadelmann, C., Salinas-Riester, G., Weber, M. S., Prinz, M., Brueck, W., Eggen, B. J. L., Boddeke, H. W. G. M., Priller, J. & Hanisch, U-K., Apr-2016, In : Glia. 64, 4, p. 635-649 15 p.

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  • CD14 is a key organizer of microglial responses to CNS infection and injury

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DOI

  • Hana Janova
  • Chotima Boettcher
  • Inge R. Holtman
  • Tommy Regen
  • Denise van Rossum
  • Alexander Goetz
  • Anne-Sophie Ernst
  • Christin Fritsche
  • Ulla Gertig
  • Nasrin Saiepour
  • Konrad Gronke
  • Claudia Wrzos
  • Sandra Ribes
  • Simone Rolfes
  • Jonathan Weinstein
  • Hannelore Ehrenreich
  • Tobias Pukrop
  • Jens Kopatz
  • Christine Stadelmann
  • Gabriela Salinas-Riester
  • Martin S. Weber
  • Marco Prinz
  • Wolfgang Brueck
  • Bart J. L. Eggen
  • Hendrikus W. G. M. Boddeke
  • Josef Priller
  • Uwe-Karsten Hanisch

Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon -mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced CNS responses to bacterial infection, traumatic and ischemic injuries, since CD14 deficiency causes either hypo- or hyperinflammation, insufficient or exaggerated immune cell recruitment or worsened stroke outcomes. While CD14 orchestrates functions of TLR4 and related immune receptors, it is itself regulated by TLR and non-TLR systems to thereby fine-tune microglial damage-sensing capacity upon infectious and non-infectious CNS challenges.

Original languageEnglish
Pages (from-to)635-649
Number of pages15
JournalGlia
Volume64
Issue number4
Publication statusPublished - Apr-2016

    Keywords

  • chemokines, cytokines, inflammation, monocytes, neutrophils, Toll-like receptor, damage, RECEPTOR 4, I INTERFERON, BRAIN, CELLS, LPS, INFLAMMATION, ACTIVATION, LIPOPOLYSACCHARIDE, RECRUITMENT, MACROPHAGES

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