Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.
Por:
Grasset EK, Chorny A, Casas-Recasens S, Gutzeit C, Bongers G, Thomsen I, Chen L, He Z, Matthews DB, Oropallo MA, Veeramreddy P, Uzzan M, Mortha A, Carrillo J, Reis BS, Ramanujam M, Sintes J, Magri G, Maglione PJ, Cunningham-Rundles C, Bram RJ, Faith J, Mehandru S, Pabst O and Cerutti A
Publicada:
31 jul 2020
Resumen:
The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.
Filiaciones:
Grasset EK:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 77 Stockholm, Sweden
Chorny A:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Casas-Recasens S:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Gutzeit C:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Thomsen I:
Institute of Molecular Medicine, Aachen University, Aachen D-52074, Germany
Chen L:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
He Z:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Matthews DB:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Oropallo MA:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Veeramreddy P:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Uzzan M:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Mortha A:
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada
:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
IrsiCaixa, Hospital Germans Trias i Pujol, Badalona 08916, Spain
Reis BS:
Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY 10065, USA
Ramanujam M:
Immunology and Respiratory Disease Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, USA
Sintes J:
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona 08003, Spain
Magri G:
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona 08003, Spain
Maglione PJ:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Cunningham-Rundles C:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Bram RJ:
Departments of Pediatrics and Immunology, Mayo Clinic, Rochester, MN 55905, USA
Faith J:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Mehandru S:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Pabst O:
Institute of Molecular Medicine, Aachen University, Aachen D-52074, Germany
Cerutti A:
Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona 08003, Spain
Catalan Institute for Research and Advanced Studies (ICREA), Barcelona 08003, Spain
Green Accepted
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