TLT-1 Promotes Platelet–Monocyte Aggregate Formation to Induce IL-10–Producing B Cells in Tuberculosis

Abstract

The immunoregulation of platelets and platelet–monocyte aggregates (PMAs) is increasingly recognized, but it roles in tuberculosis (TB) remain to be elucidated. In this study, we found that CD14+CD41+ PMAs were increased in peripheral blood of patients with active TB. CD14+CD41+ PMAs highly expressed triggering receptors expressed on myeloid cells (TREMs)-like transcript-1 (TLT-1), P-selectin (CD62P), and CD40L. Our in vitro study found that platelets from patients with active TB aggregate with monocytes to induce IL-1β and IL-6 production by monocytes. Importantly, we identified that TLT-1 was required for formation of PMAs. The potential TLT-1 ligand was expressed and increased on CD14+ monocytes of patients with TB determined by using TLT-1 fusion protein (TLT-1 Fc). Blocking of ligand–TLT-1 interaction with TLT-1 Fc reduced PMA formation and IL-1β and IL-6 production by monocytes. Further results demonstrated that PMAs induced IL-10 production by B cells (B10) dependent on IL-1β, IL-6, and CD40L signals in a coculture system. Moreover, TLT-1 Fc treatment suppressed B10 polarization via blocking PMA formation. Taking all of these data together, we elucidated that TLT-1 promoted PMA-mediated B10 polarization through enhancing IL-1β, IL-6, and CD40L origin from PMAs, which may provide potential targeting strategies for TB disease treatment.