title: 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.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Current address: Department of Internal Medicine-Rheumatology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI, USA.
authors.forename: L E P M
authors.initials: LEPM
authors.lastname: van der Vlugt
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Obieglo
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Ozir-Fazalalikhan
authors.affiliation: Institute of Infection Immunology, Twincore/Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Straße 7, 30625 Hanover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Current address: Institute for Parasitology, Justus-Liebig-University Giessen, Schubertstrasse 81, Giessen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Haeberlein
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: H.H.Smits@lumc.nl.
authors.forename: H H
authors.initials: HH
authors.lastname: Smits
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005260:Female; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D012552:Schistosomiasis / Q000150:complications / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D016753:Interleukin-10
keywords: Allergic airway inflammation; Lung; Regulatory B cell; Schistosoma; Th2 response