TY - JOUR
T1 - Differentiation of primary adult microglia alters their response to TLR8-mediated activation but not their capacity as APC
AU - Zuiderwijk-Sick, Ella A
AU - van der Putten, Céline
AU - Bsibsi, Malika
AU - Deuzing, Ilona P
AU - de Boer, Willem
AU - Persoon-Deen, Carla
AU - Kondova, Ivanela
AU - Boven, Leonie A
AU - van Noort, Johannes M
AU - 't Hart, Bert A
AU - Amor, Sandra
AU - Bajramovic, Jeffrey J
PY - 2007/11/15
Y1 - 2007/11/15
N2 - Activated 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.
AB - Activated 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.
KW - Animals
KW - Antigen-Presenting Cells
KW - Bone Marrow Cells
KW - Cell Differentiation
KW - Cell Lineage
KW - Cell Proliferation
KW - Cell Separation
KW - Enzyme-Linked Immunosorbent Assay
KW - Female
KW - Flow Cytometry
KW - Granulocyte-Macrophage Colony-Stimulating Factor
KW - Lymphocyte Culture Test, Mixed
KW - Macaca mulatta
KW - Macrophage Activation
KW - Macrophage Colony-Stimulating Factor
KW - Male
KW - Microglia
KW - Phagocytosis
KW - RNA, Messenger
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Toll-Like Receptor 8
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/glia.20572
DO - 10.1002/glia.20572
M3 - Article
C2 - 17823968
VL - 55
SP - 1589
EP - 1600
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 15
ER -