SerpinB2 mediated regulation of macrophage function during enteric infection

Gut Microbes. Mar-Apr 2014;5(2):254-8. doi: 10.4161/gmic.28093. Epub 2014 Feb 5.

Abstract

Host defense is an orchestrated response involving changes in the expression of receptors and release of mediators from both immune and structural cells. There is a growing recognition of the important role of proteolytic pathways for the protective immune response to enteric pathogens. Enteric nematode infection induces a type 2 immune response with polarization of macrophages toward the alternatively activated phenotype (M2). The Th2 cytokines, IL-4, and IL-13, induce a STAT6-dependent upregulation of the expression of the protease inhibitor, serpinB2, which protects macrophages from apoptosis. M2 are critical to worm clearance and a novel role for serpinB2 is its regulation of the chemokine, CCL2, which is necessary for monocyte and/or macrophage influx into small intestine during infection. There is a growing list of factors including immune (LPS, Th2 cytokines) as well as hormonal (gastrin, 5-HT) that are linked to increased expression of serpinB2. Thus, serpinB2 represents an immune regulated factor that has multiple roles in the intestinal mucosa.

Keywords: Th2 cytokines; enteric nematode infection; macrophage; plasminogen activation system; serpinB2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Gastrointestinal Tract / metabolism*
  • Gastrointestinal Tract / parasitology*
  • Humans
  • Macrophages / metabolism*
  • Macrophages / parasitology*
  • Monocytes / metabolism
  • Nematode Infections / metabolism*
  • STAT6 Transcription Factor / metabolism
  • Th2 Cells / metabolism

Substances

  • Cytokines
  • STAT6 Transcription Factor
  • STAT6 protein, human