Differentiation of primary adult microglia alters their response to TLR8‐mediated activation but not their capacity as APC

GLIA - Tập 55 Số 15 - Trang 1589-1600 - 2007
Ella A. Zuiderwijk‐Sick1, Céline van der Putten1, Malika Bsibsi2, Ilona P. Deuzing1, Willem de Boer1, C. Persoon-Deen2, Ivanela Kondova3, Leonie A. Boven4, Johannes M. van Noort2, Bert A. ’t Hart5, Sandra Amor5, Jeffrey J. Bajramović1
1Alternatives Unit, Biomedical Primate Research Centre, Rijswijk, the Netherlands
2Department of Biosciences, TNO Quality of Life, Leiden, The Netherlands
3Animal Science Department, Biomedical Primate Research Centre, Rijswijk, The Netherlands
4Department of Immunology and MS Centre ErasMS, Erasmus MC, Rotterdam, The Netherlands
5Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands

Tóm tắt

AbstractActivated microglia are found in a variety of neuroinflammatory disorders where they have attributed roles as effector as well as antigen‐presenting cells (APC). Critical determinants for the multifaceted role of microglia are the differentiation potential of microglia and their mode of activation. In this study, we have investigated the effects of M‐CSF and GM‐CSF‐mediated differentiation of adult primate microglia on their cellular phenotype, antigen presentation, and phagocytic function as well as on Toll‐like receptor (TLR)‐mediated responses. We show that although cell morphology and expression levels of activation markers were markedly different, differentiation with either factor yielded microglia that phenotypically and functionally resemble macrophages. Both M‐CSF and GM‐CSF‐differentiated microglia were responsive to TLR1/2, 2, 3, 4, 5, 6/2, and 8‐mediated activation, but not to TLR7 or 9‐mediated activation. Intriguingly, M‐CSF‐differentiated microglia expressed higher levels of TLR8‐encoding mRNA and protein, and produced larger amounts of proinflammatory cytokines in response to TLR8‐mediated activation as compared to GM‐CSF‐differentiated microglia. While differentiation of adult microglia by growth factors that can be produced endogenously in the central nervous system is thus unlikely to change their APC function, it can alter their innate responses to infectious stimuli such as ssRNA viruses. Resident primate microglia may thereby help shape rather than initiate adaptive immune responses. © 2007 Wiley‐Liss, Inc.

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GLIA

Tập 55 Số 15

1589-1600

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