The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model.

Abstract

BACKGROUND:

The exact mechanism of the inflammatory changes occurring during the development of Behçet's disease (BD) remains unclear.

OBJECTIVE:

We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model.

METHODS:

The classical vs. alternative activated macrophage ratio (M1/M2 ratio) was calculated by analyzing the surface markers CD16/32 and CD23 as M1 and M2 markers, respectively, by flow cytometry. mRNA expression of interferon (IFN)-γ and interleukin (IL)-6 as M1 and arginase-1, FIZZ-1, and MHC-II as M2 markers were analyzed by reverse transcription-polymerase chain reaction. Cytokine levels were assessed by enzyme-linked immunosorbent assay.

RESULTS:

The M1 phenotype was upregulated in BD mice, and an increased M1/M2 ratio was observed compared to that in asymptomatic BD normal and normal healthy mice. Recombinant (r)IFN-γ significantly increased the M1/M2 ratio (1.74±0.42) compared with that of rIL-4 (0.83±0.20). BD mice treated with rIL-4 showed a decreased M1/M2 ratio (1.2±0.3) compared to that of the rIFN-γ- (2.1±2.3) treated group and also showed ameliorated BD symptoms accompanied by downregulation of IL-17 and IL-6 and up-regulation of IL-4.

CONCLUSION:

Therefore, modulation of macrophage phenotypes could be an effective therapeutic approach for treating BD in the future.