Mycobacterium tuberculosis protein Rv2220 induces maturation and activation of dendritic cells

Cell Immunol. 2018 Jun:328:70-78. doi: 10.1016/j.cellimm.2018.03.012. Epub 2018 Mar 31.

Abstract

Tuberculosis remains a serious health problem worldwide. Characterization of the dendritic cell (DC)-activating mycobacterial proteins has driven the development of effective TB vaccine candidates besides improving the understanding of immune responses. Some studies have emphasized the essential role of protein Rv2220 from M. tuberculosis in mycobacterial growth. Nonetheless, little is known about cellular immune responses to Rv2220. In this study, our aim was to test whether protein Rv2220 induces maturation and activation of DCs. Rv2220-activated DCs appeared to be in a mature state with elevated expression of relevant surface molecules and proinflammatory cytokines. DC maturation caused by Rv2220 was mediated by MAPK and NF-κB signaling pathways. Specifically, Rv2220-matured DCs induced the expansion of memory CD62LlowCD44highCD4+ T cells in the spleen of mycobacteria-infected mice. Our results suggest that Rv2220 regulates host immune responses through maturation of DCs, a finding that points to a new vaccine candidate against tuberculosis.

Keywords: Dendritic cell activation; Immune response; Mycobacterium tuberculosis; Rv2220; glnA1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / metabolism
  • Cell Differentiation / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Immunity, Cellular / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity
  • NF-kappa B / metabolism
  • Primary Cell Culture
  • Signal Transduction
  • Th1 Cells / immunology
  • Tuberculosis / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • NF-kappa B
  • Mitogen-Activated Protein Kinases