Sj HSP 60 induces CD 4+ CD 25+Foxp3+ Tregs via TLR 4‐Mal‐drived production of TGF ‐β in macrophages

CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a pivotal role in limiting immunopathological damage to host organs after schistosome infection. Transforming growth factor‐β (TGF‐β) is an essential factor for the periphery conversion of CD4+CD25− T cells into CD4+CD25+Foxp3+ Tregs by inducing the key transcription factor Foxp3. Antigen presenting cells (APCs), which highly express TGF‐β, are involved in parasite antigen‐induced Treg conversion in peripheral. However, the mechanisms underlying high TGF‐β induction in APCs by parasite antigens remain to be clarified during schistosome infection. Here, we demonstrated that Schistosoma japonicum stress protein, heat shock protein 60 (SjHSP60), promoted TGF‐β production in macrophages (Mφ). Furthermore, we showed that activation of TLR4‐Mal (MyD88 adaptor‐like protein) signaling by SjHSP60 is necessary for induction of TGF‐β expression in Mφ, which subsequently promoted Treg induction. Our results not only demonstrate a novel mechanism of TGF‐β production in Mφ for inducing Tregs in mice with schistosomiasis, but also allude to the possibility of targeting parasite stress protein for potential therapeutics.