Publication

Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia

Scheffel, J., Regen, T., Van Rossum, D., Seifert, S., Ribes, S., Nau, R., Parsa, R., Harris, R. A., Boddeke, H. W. G. M., Chuang, H-N., Pukrop, T., Wessels, J. T., Juergens, T., Merkler, D., Brueck, W., Schnaars, M., Simons, M., Kettenmann, H. & Hanisch, U-K., Dec-2012, In : Glia. 60, 12, p. 1930-1943 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Joerg Scheffel
  • Tommy Regen
  • Denise Van Rossum
  • Stefanie Seifert
  • Sandra Ribes
  • Roland Nau
  • Roham Parsa
  • Robert A. Harris
  • Hendrikus W. G. M. Boddeke
  • Han-Ning Chuang
  • Tobias Pukrop
  • Johannes T. Wessels
  • Tanja Juergens
  • Doron Merkler
  • Wolfgang Brueck
  • Mareike Schnaars
  • Mikael Simons
  • Helmut Kettenmann
  • Uwe-Karsten Hanisch

The sentinel and immune functions of microglia require rapid and appropriate reactions to infection and damage. Their Toll-like receptors (TLRs) sense both as threats. However, whether activated microglia mount uniform responses or whether subsets conduct selective tasks is unknown. We demonstrate that murine microglia reorganize their responses to TLR activations postnatally and that this process comes with a maturation of TLR4-organized functions. Although induction of MHCI for antigen presentation remains as a pan-populational feature, synthesis of TNFa becomes restricted to a subset, even within adult central nervous system regions. Response heterogeneity is evident ex vivo, in situ, and in vivo, but is not limited to TNFa production or to TLR-triggered functions. Also, clearance activities for myelin under physiological and pathophysiological conditions, IFN >> factors reveal dissimilar microglial contributions. Notably, response heterogeneity is also confirmed in human brain tissue. Our findings suggest that microglia divide by constitutive and inducible capacities. Privileged production of inflammatory mediators assigns a master control to subsets. Sequestration of clearance of endogenous material versus antigen presentation in exclusive compartments can separate potentially interfering functions. Finally, subsets rather than a uniform population of microglia may assemble the reactive phenotypes in responses during infection, injury, and rebuilding, warranting consideration in experimental manipulation and therapeutic strategies. (c) 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)1930-1943
Number of pages14
JournalGlia
Volume60
Issue number12
Publication statusPublished - Dec-2012

    Keywords

  • cytokines, heterogeneity, MHC, myelin, phagocytosis, phenotype, subpopulation, TLR, IN-VIVO, LIPOPOLYSACCHARIDE RECOGNITION, MACROPHAGE ACTIVATION, MULTIPLE-SCLEROSIS, BRAIN, CELLS, DISTINCT, INFLAMMATION, LPS, IDENTIFICATION

ID: 5704366