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

• DOI: 10.1016/j.ijpara.2017.02.002
• Publication Date: 2017-04-04T04:22:41Z
• Authors: L.E.P.M. van der ...; K. Obieglo; A. Ozir-Fazalalikhan; T. Sparwasser; S. Haeberlein; H.H. Smits
• Keywords: 0301 basic medicine; B-Lymphocytes, Regulatory; Regulatory B cell; Adoptive Transfer; Th2 response; Immunophenotyping; Interleukin-10; Specific Pathogen-Free Organisms; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Th2 Cells; Respiratory Hypersensitivity; Schistosoma; Animals; Cytokines; Schistosomiasis; Female; Allergic airway inflammation; Bronchoalveolar Lavage Fluid; Lung

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.