Leishmania Regulated MTDH Expression to Suppress Dendritic Cells

Tohoku J Exp Med. 2022 Dec 14;259(1):57-63. doi: 10.1620/tjem.2022.J091. Epub 2022 Nov 3.

Abstract

This study aimed to investigate the correlation between Leishmania infection and dendritic cell infiltration and explore the underlying molecular mechanism how Leishmania infection regulates dendritic cell infiltration. Three datasets, GSE63931, GSE80008 and GSE77528 were combined and their batch effects were removed by Combat function in sva R package. Immune cell infiltrations were estimated using the Microenvironment Cell Populations-counter (MCP-counter) R package. Statistical results were verified by Student's t test. The differential expression of metadherin (MTDH) was identified by Limma R package. The correlation between MTDH expression and dendritic cell infiltration was estimated by Pearson's product moment correlation coefficient. GDS5086 was used to explore MTDH expression pattern in dendritic cells infected with Leishmania. Compared with normal samples, 5 types of immune cells showed differential infiltration in leishmaniasis samples, including T cells, CD8+ T cells, dendritic cells, cytotoxic lymphocytes and B lineage cells. Among these, only DCs were significantly suppressed in leishmaniasis samples. Notably, MTDH expression was differential between leishmaniasis and normal samples. There was a significant correlation between MTDH expression and dendritic cell infiltration. In conclusion, these results demonstrate that Leishmania infection leads to the downregulation of MTDH expression and the suppression of dendritic cell infiltration.

Keywords: Leishmania; MTDH; dendritic cell; gene expression; infiltration.

MeSH terms

  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Adhesion Molecules* / metabolism
  • Dendritic Cells / metabolism
  • Humans
  • Leishmania* / metabolism
  • Membrane Proteins / metabolism
  • RNA-Binding Proteins

Substances

  • Cell Adhesion Molecules
  • RNA-Binding Proteins
  • Membrane Proteins
  • MTDH protein, human