Schistosome-induced pulmonary B cells inhibit allergic airway inflammation and display a reduced Th2-driving function

Abstract

Chronic schistosome infections protect against allergic airway inflammation (AAI) via the induction of IL-10-producing splenic regulatory B (Breg) cells. Previous experiments have demonstrated that schistosome-induced pulmonary B cells can also reduce AAI, but act independently of IL-10. We have now further characterized the phenotype and inhibitory activity of these protective pulmonary B cells. We excluded a role for regulatory T (Treg) cell induction as putative AAI-protective mechanisms. Schistosome-induced B cells showed increased CD86 expression and reduced cytokine expression in response to Toll-like receptor (TLR) ligands compared with control B cells. To investigate the consequences for T cell activation we cultured ovalbumin (OVA)-pulsed, schistosome-induced B cells with OVA-specific transgenic T cells and observed less Th2 cytokine expression and T cell proliferation compared with control conditions. This suppressive effect was preserved even under optimal T cell stimulation by anti-CD3/28. Blocking of the inhibitory cytokines IL-10 or TGF-β only marginally restored Th2 cytokine induction. These data suggest that schistosome-induced pulmonary B cells are impaired in their capacity to produce cytokines to TLR ligands and to induce Th2 cytokine responses independent of their antigen-presenting function. These findings underline the presence of distinct B cell subsets with different stimulatory or inhibitory properties even if induced by the same type of helminth.

Wuchereria bancrofti-infected individuals harbor distinct IL-10-producing regulatory B and T cell subsets which are affected by anti-filarial treatment

“…Besides Tregs, the expanding family of Bregs and their role in suppressing pathological immune responses and during helminth infections has recently been recognized [11, 14, 43, 44]. For example, it was shown that various helminth infections induce IL-10-producing Breg populations [12–14, 45] which were shown to be antigen-specific during chronic schistosomiasis [46, 47], but the distinct role of Breg populations during W . bancrofti infection has remained largely unclear.…”

Helminth Therapy for Immune-Mediated Inflammatory Diseases: Current and Future Perspectives

“…Multiple studies have shown that infection with helminths can be accompanied by the proliferation of Breg cells. [130][131][132] IL-10 + Breg cells not only induce expansion of IL-10 + Treg cells and maintenance of FoxP3 + Treg cells, but also inhibit inflammatory response in OVA model of asthma. 133 IPSE/alpha-1 of Schistosoma mansoni can induce Breg cells in mice and humans in vitro.…”

Changes in pro inflammatory and regulatory immune responses during controlled human schistosome infection and the development of clinical symptoms

“…Here, we have shown an enhanced regulatory response at week 8, including an increase in serum IL-10 levels. IL-10 has crucial regulatory and host-protective roles in schistosomiasis ( 39–42 ). Here we identified CD38 + DN T cells as key producers of IL-10 at week 8 post infection and revealed a novel correlation between this subset and levels of the pro-inflammatory cytokine IL-18 ( 43 ).…”