Podoplanin Drives Motility of Active Macrophage via Regulating Filamin C During Helicobacter pylori Infection

Front Immunol. 2021 Oct 11:12:702156. doi: 10.3389/fimmu.2021.702156. eCollection 2021.

Abstract

Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In addition, interleukin-1β production was significantly declined in the absence of Pdpn, suggesting a role of Pdpn in orchestrating inflammation during H. pylori infection besides cellular migration. Together, our findings unravel the Pdpn network that modulates movement of active macrophages.

Keywords: Filamin C; Helicobacter pylori; cell migration; interleukin-1β; macrophage; podoplanin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / immunology*
  • Filamins / metabolism*
  • Helicobacter Infections / immunology
  • Helicobacter pylori
  • Humans
  • Macrophages / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • RAW 264.7 Cells
  • THP-1 Cells

Substances

  • Filamins
  • Gp38 protein, mouse
  • Membrane Glycoproteins
  • PDPN protein, human