Mast cells activate MDSC to promote inflammation (177.2)

Abstract

Abstract Mast cells play an important role in promoting inflammation, controlling parasitic infection, and potentiating allergic disease. Conversely, myeloid-derived suppressor cells (MDSC) are found in tumor-bearing individuals and in models of septic shock, where they are known to have regulatory effect. We aimed to determine a possible role for interactions between MDSC and mast cells and the effect of these interactions in a mouse model of parasitic infection. Surprisingly, co-culture of these cells resulted in a drastic increase in pro-inflammatory mediator release, which was attributed entirely to MDSC. Depletion of MDSC from mice infected with Nippostrongylus brasiliensis resulted in delayed worm expulsion and a drastically increased intestinal worm burden. Conversely, this inflammatory role of MDSC seems detrimental when inflammation is chronic, as MDSC depletion in an airway hyperresponsiveness model decreased the pathology of this disease. Interestingly, we have found that mast cell conditioned-media activates both the STAT3 and ERK pathways in MDSC, which could represent a novel means of pro-inflammatory cytokine induction in MDSC. We therefore conclude that mast cells can reprogram MDSC to a pro-inflammatory phenotype, suggesting that the evolutionary purpose of these suppressive cells may be to potentiate inflammatory Th2 responses necessary for parasite expulsion.