SPY1 vaccination activated Foxp3, increasing the frequency of CD4+CD25+Foxp3+ Tregs during vaccination; SPY1 elevated Smad2/3 and phosphor-Smad2/3 downregulated a negative signal by Smad7 during live bacterial infection (Smad 1–9 regulate TGF-β receptor signaling) [85]. The gene discussed is SPDYA; the disease is bacterial infectious disease.