Induction of Anti-inflammatory Cytokines in CD11b- and Gr-1- Positive Cells after Neuropathogenic Coronaviral Infection

Masatoshi Kakizaki,Rihito Watanabe,Akira Togayachi

doi:10.4172/2576-389x.1000112

Abstract

Mu-3 virus (Mu-3), a neuropathogenic strain of the mouse hepatitis virus, induces the apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus at 4 days post-inoculation (dpi), without showing destructive changes or viral invasion there at 3 dpi. Since it has been considered that the apoptotic lesions occur through the indirect effects of infection, local expression of cytokines was examined in the brain in our previous study, revealing that the anti-inflammatory cytokine IL-10 is produced by pyramidal neurons of CA2 and CA3 after infection. However, infection of primary brain culture failed to elevate IL-10 production. Therefore, in order to examine whether Mu-3 infection elevates IL-10 production, CD11b-expressing Peritoneal Exudate Cells (PECs) were used, which showed an increased level of IL-10 production in the supernatant of PEC culture after infection. The finding that IL-10-producing cells expressed Lewis X (Lex) supports our previous hypothesis that Lex expression is involved in the immunosuppressive state induced by viral infection. In addition, in combination with an experiment involving ex vivo infection, it was indicated that Mu-3 elicits M2 macrophages or Gr-1+CD11b+ Myeloid- Derived Suppressor Cells (MDSCs) that produce IL-10 and TGF-β to circumvent the host immune response after infection.

Highlights

The Mutant virus Mu-3, isolated from the srr7 virus [1,2], causes the apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus after infection [3]
Thereafter, we examined the involvement of antiinflammatory cytokines, and found that IL-10 is expressed in pyramidal neurons in CA2 and CA3 subregions of the hippocampus [6]
Because an examination using primary brain cultures failed to detect the production of anti-inflammatory cytokines [6], the in vitro inducibility of cytokines by Mu-3 infection was studied using Peritoneal Exudate Cells (PECs), which produce measurable IL-10 under the Endotoxin Tolerance (ET) state [13], in order to examine whether Mu-3 infection is able to trigger the production of anti-inflammatory cytokines

Summary

Introduction

The Mutant virus Mu-3, isolated from the srr virus (srr7) [1,2], causes the apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus after infection [3]. The involvement of anti-inflammatory cytokines in the development of the lesions observed in the hippocampus after infection with Mu-3 corresponds to our previous findings that Mu-3, srr, and its maternal clone, JHM virus strain (JHMV) cl-2 virus (cl-2), induce an immunosuppressive state in the infected mice, which have a shrunk spleen with reduced cell population and the neuropathology showing very low-level inflammatory cell infiltration in the brain parenchyma in spite of a wide area of brain damage [2,7,8]. The leukocytes derived from the infected mice show unresponsiveness to the stimulation by Lipopolysaccharide (LPS) [9,10], mimicking the state in Endotoxin Tolerance (ET), or LPS tolerance, where a population of CD11bmidGr-1mid suppressor Monocytes/Macrophages (Mo/Mas) plays a central role, secreting the anti-inflammatory cytokines IL-10 and TGF-β [11]

Methods

Results

Conclusion