Identification and exploration of a new M2 macrophage marker MTLN in alveolar echinococcosis

Int Immunopharmacol. 2024 Apr 20:131:111808. doi: 10.1016/j.intimp.2024.111808. Epub 2024 Mar 7.

Abstract

The pathogen of alveolar echinococcosis (AE) is Echinococcus multilocularis (E. multilocularis), which has the characteristics of diffuse infiltration and growth and has a high mortality rate. At present, the role of macrophages in AE infection has attracted more and more attention, but the new biomarkers and polarization mechanisms of macrophages are rarely studied. In this study, CIBERSORT and WGCNA algorithms were used to establish a weighted gene co-expression network, and MTLN was identified as a biological marker of M2-type macrophages, which participated in energy metabolism of macrophages and mediated inflammatory response, but the role of MTLN in AE was not studied. In this study, liver tissue samples from AE patients were collected and immunofluorescence co-localization showed the relationship between MTLN and macrophage distribution. E. multilocularis infected mouse model was established to analyze the expression of MTLN, liver fibrosis, and inflammatory reaction after E. multilocularis infection. The cell experiment simulated the liver microenvironment of E. multilocularis infected human body and analyzed the expression of MTLN by QRT-PCR and western blot in vitro. The data showed that liver fibrosis occurred in AE patients, and MTLN was activated near the focus. After E. multilocularis infected mice, the expression of MTLN increased with time. In the cell experiment, after the antigen of E. multilocularis protoscolex stimulated normal liver cells, the expression of MTLN increased 48 h, at this time, M2 was up-regulated and M1 was down-regulated. Therefore, MTLN may be the key gene to regulate the polarization of M2 macrophages and cause fibrosis.

Keywords: Alveolar echinococcosis; E. multilocularis infection; Hepatic fibrosis; MTLN; Macrophage polarization.

MeSH terms

  • Animals
  • Echinococcosis* / genetics
  • Echinococcus multilocularis* / genetics
  • Hepatocytes
  • Humans
  • Liver Cirrhosis
  • Mice

Supplementary concepts

  • Alveolar echinococcosis