Human mast cell responses via TLR4 and FceRI

Objectives: Rodent Mast cells (MCs) are reported to play a pivotal role in both innate and adaptive immunity. However there is so far no evidence that human MCs are involved in innate immunity. Methods: and Results: We studied expression of TLR4 on human adult peripheral blood derived-cultured MCs and human lung MCs. By using real-time RT-PCR and flow cytometory, we found that expression of TLR4 was up-regulated by IFN-g. We confirmed that LPS induced TNF-a production by MCs via TLR4. To systematically explore how human MCs modulate the immune system following TLR4-mediated activation and FceRI aggregation, we performed high-density oligonucleotide probe arrays to compare the LPS-induced gene expression profile with IgE/a-IgE-mediated profile in MCs. Both a shared core response, and LPS- or anti-IgE-specific programs of gene expression were observed. Interestingly, MCs exhibited an antiviral response gene program in response to IFN-g and LPS sustained that expression. Furthermore, we compared LPS-induced gene expression profile of MCs with that of human peripheral blood mononuclear cells. LPS-stimulated MCs specifically included a subset of genes that induced a Th2 cytokine and chemokines, that recruit Th2 cells and eosinophils. Conclusions: These results reveal that human MCs express tailored pathogen- and antigen-specific immune responses and that human MCs may play important roles in innate and adaptive immunity.