Modulation of Microglial Cell Fcγ Receptor Expression Following Viral Brain Infection.
Fcγ receptors (FcγRs) for IgG couple innate and adaptive immunity through activation of effector cells by antigen-antibody complexes. We investigated relative levels of activating and inhibitory FcγRs on brain-resident microglia following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of microglial cells obtained from infected brain tissue demonstrated that activating FcγRs were expressed maximally at 5 d post-infection (dpi), while the inhibitory receptor (FcγRIIB) remained highly elevated during both acute and chronic phases of infection. The highly induced expression of activating FcγRIV during the acute phase of infection was also noteworthy. Furthermore, in vitro analysis using cultured primary microglia demonstrated the role of interferon (IFN)γ and interleukin (IL)-4 in polarizing these cells towards a M1 or M2 phenotype, respectively. Microglial cell-polarization correlated with maximal expression of either FcγRIV or FcγRIIB following stimulation with IFNγ or IL-4, respectively. Finally, we observed a significant delay in polarization of microglia towards an M2 phenotype in the absence of FcγRs in MCMV-infected Fcer1g and FcgR2b knockout mice. These studies demonstrate that neuro-inflammation following viral infection increases expression of activating FcγRs on M1-polarized microglia. In contrast, expression of the inhibitory FcγRIIB receptor promotes M2-polarization in order to shut-down deleterious immune responses and limit bystander brain damage.
Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Priyanka
P
Chauhan
Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Shuxian
S
Hu
Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Wen S
WS
Sheng
Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Sujata
S
Prasad
Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
James R
JR
Lokensgard
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006566:Herpesviridae Infections / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018146:Muromegalovirus; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*
C080571:Fc gamma receptor IIB; D017452:Receptors, IgG; D015847:Interleukin-4; D007371:Interferon-gamma