IL‐10 expression in pyramidal neurons after neuropathogenic coronaviral infection

Abstract

The apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus is induced after infection with Mu-3 virus (Mu-3), a neuropathogenic strain of the JHM virus (JHMV), at 4-5 days post-inoculation (dpi). The viral antigens in the hippocampus are mainly found in the CD11b-positive cells distributed in the stratum oriens located outside the pyramidal layer, and only a few pyramidal neurons are infected. Furthermore, the apoptotic cells, indicated as showing caspase 3 (Cas3) activation, consist of a high number of uninfected cells. Therefore, it is considered that the apoptotic lesions occur through the indirect effects of infection, and not as a result of direct infection with Mu-3, similar to the reported neuronal apoptosis in the hippocampus after other types of infection. The apoptosis in the pyramidal neurons is accompanied by various types of proinflammatory cytokines depending on the causative agents. Thus, the local expression of proinflammatory cytokines was studied, revealing no correlation in the distribution of cytokine expression with the subregions showing apoptosis. However, the anti-inflammatory cytokine IL-10 was produced by pyramidal neurons of CA2 and CA3 at 3 dpi when there is no destructive change or viral invasion in the hippocampus.

IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury

“…The results indicated that the protein level of spinal Nrf2 was increased at 2 h post intraperitoneal injection of 200 mg/kg 4-OI ( Figures 9C, D ). Since both the neurons ( 36 , 37 ) and microglia ( 38 ) could produce the IL-10, then we used the N2A cells and BV2 cells to mimic neurons and microglia respectively. We found that after the treatment of 4-OI and 4-OI+LPS, the IL-10 released from the N2A cells was increased compared to that in the vehicle group ( Figure 9E ).…”

“…Consistent with this, the IL-10 expression in ipsilateral spinal cord was increased in neurons after systemic injection of 4-OI in CCI mice. Although myeloid cells are the main source of IL-10, there are some studies indicating the IL-10 also can be produced in neurons ( 36 , 37 ), neuronal cell line ( 53 ), and neural stem cells ( 54 ). So, it needs further investigation to explain why 4-OI fails to promote the expression of IL-10 in microglia and elucidate the specific regulation mechanisms of itaconate on neuronal IL-10 production.…”