Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and XXXX .

@entity19 @entity1618 @entity1200 @entity16966 @entity630
Emerging evidence suggests critical roles for @entity16966 in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce @entity1200 . First, zymosan induces DCs to secrete abundant @entity1618 but little IL-6 and IL-12(p70). Induction of @entity1618 is dependent on TLR2- and dectin-1-mediated activation of ERK MAPK via a mechanism independent of the activation protein 1 (AP-1) transcription factor c-Fos. Such DCs stimulate antigen-specific CD4+ T cells poorly due to @entity1618 and the lack of IL-6. Second, zymosan induces F4-80+ macrophages in the splenic red pulp to secrete TGF-beta. Consistent with these effects on @entity16966 , injection of zymosan plus OVA into @entity19 results in OVA-specific T cells that secrete little or no @entity630 or Th2 cytokines, but secrete robust levels of @entity1618 , and are unresponsive to challenge with OVA plus adjuvant. Finally, coinjection of zymosan with OVA plus LPS suppresses the response to OVA via a mechanism dependent on @entity1618 , TGF-beta, and lack of IL-6. Together, our data demonstrate that zymosan stimulates @entity1618 + IL-12(p70)- IL-6low regulatory DCs and TGF-beta+ macrophages to induce @entity1200 . These data suggest several targets for pharmacological modulation of immune responses in various clinical settings.
