Modulation of Microglial Cell Fc gamma Receptor Expression Following Viral Brain Infection

作者：Chauhan Priyanka; Hu Shuxian; Sheng Wen S; Prasad Sujata; Lokensgard James R^*

来源：Scientific Reports, 2017, 7(1): 41889.

DOI：10.1038/srep41889

Fc gamma receptors (Fc gamma Rs) for IgG couple innate and adaptive immunity through activation of effector cells by antigen-antibody complexes. We investigated relative levels of activating and inhibitory Fc gamma Rs on brain-resident microglia following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of microglial cells obtained from infected brain tissue demonstrated that activating Fc gamma Rs were expressed maximally at 5 d post-infection (dpi), while the inhibitory receptor (Fc gamma RIIB) remained highly elevated during both acute and chronic phases of infection. The highly induced expression of activating Fc gamma RIV during the acute phase of infection was also noteworthy. Furthermore, in vitro analysis using cultured primary microglia demonstrated the role of interferon (IFN)gamma and interleukin (IL)-4 in polarizing these cells towards a M1 or M2 phenotype, respectively. Microglial cell-polarization correlated with maximal expression of either Fc gamma RIV or Fc.RIIB following stimulation with IFN gamma or IL-4, respectively. Finally, we observed a significant delay in polarization of microglia towards an M2 phenotype in the absence of Fc gamma Rs in MCMV-infected Fcer1g and FcgR2b knockout mice. These studies demonstrate that neuro-inflammation following viral infection increases expression of activating Fc gamma Rs on M1-polarized microglia. In contrast, expression of the inhibitory Fc gamma RIIB receptor promotes M2-polarization in order to shut-down deleterious immune responses and limit bystander brain damage.

• 出版日期2017-2-6