GM-CSF production by non-classical monocytes controls antagonistic LPS-driven functions in allergic inflammation

Academic Article

Abstract

  • Lipopolysaccharide (LPS) can either promote or prevent T helper 2 (Th2) cell allergic responses. However, the underlying mechanism remains unknown. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by non-classical monocytes. In the absence of GM-CSF, LPS can favor pathogenic Th2 cell responses by supporting the trafficking of lung-migratory dendritic cells (mDC2s) into the lung-draining lymph node. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate monocyte-derived DCs from classical Ly6Chi monocytes that instruct mDC2s for Th2 cell suppression. Importantly, only allergens with cysteine protease activity trigger GM-CSF production by non-classical monocytes. Hence, the therapeutic effect of LPS is restricted to allergens with this enzymatic activity. Treatment with GM-CSF, however, restores the protective effects of LPS. Thus, GM-CSF produced by non-classical monocytes acts as a rheostat that fine-tunes the pathogenic and therapeutic functions of LPS.
  • Published In

  • Cell Reports  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 15288904
  • Author List

  • Kaur K; Bachus H; Lewis C; Papillion AM; Rosenberg AF; Ballesteros-Tato A; León B
  • Volume

  • 37
  • Issue

  • 13