Transcriptional response of human microglial cells to interferon-gamma.
Microglia, the resident macrophages in the central nervous system (CNS), play a pivotal role in innate and adaptive immune responses in the brain. The immune functions of microglia are regulated by cytokines, including interferon (IFN)-gamma, which is a major mediator of macrophage activation. We describe the transcriptional profile of human fetal microglial cells at 1, 6, and 24 h after IFN-gamma treatment. The results show a change in the expression of 405 genes including transcriptionally induced chemokines, IFN-gamma signaling factors, and major histocompatibility complex genes. Our results demonstrate that activation of microglia by IFN-gamma induces proinflammatory T-lymphocyte-related chemokine genes as well as genes involved in antigen presentation. As a result, signals for T-cell infiltration and antigen presentation are produced to allow for microglia-T-cell interactions that likely contribute to defense against invading pathogens. In sum, our results provide a foundation for the molecular mechanisms of the microglial response to IFN-gamma-a key to understanding cell-mediated immunity of the CNS.
Rock
R B
RB
Department of Medicine, Division of Infectious Diseases and International Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Hu
S
S
Deshpande
A
A
Munir
S
S
May
B J
BJ
Baker
C A
CA
Peterson
P K
PK
Kapur
V
V
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D018925:Chemokines / Q000032:analysis; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D005333:Fetus; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D008957:Models, Genetic; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
C111835:CCL2 protein, human; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D003470:Culture Media; D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma