Myeloid-derived suppressor cells enhance IgE-mediated mast cell responses.

Mast cells and MDSCs are increased by parasitic infection and tumor growth. We previously demonstrated that enhanced MDSC development in ADAM10 transgenic mice yielded resistance to Nb infection and that coculturing MDSCs and mast cells enhanced cytokine production. In the current work, we show that MDSC-mast cell coculture selectively enhances IgE-mediated cytokine secretion among mast cells, without increasing MDSC cytokine production. This effect was independent of cell contact and elicited by Ly6C(+) and Ly6C/G+ MDSC subsets. These interactions were functionally important. MDSC depletion with the FDA-approved drug gemcitabine exacerbated Nb or Trichinella spiralis infection and reduced mast cell-dependent AHR and lung inflammation. Adoptive transfer of MDSC worsened AHR in WT but not mast cell-deficient Wsh/Wsh mice. These data support the hypothesis that MDSCs enhance mast cell inflammatory responses and demonstrate that this interaction can be altered by an existing chemotherapeutic.