| Title: |
Gut IgA functionally interacts with systemic IgG to enhance antipneumococcal vaccine responses |
| Authors: |
Gutzeit, C.; Grasset, E.K.; Matthews, D.B.; Maglione, P.J.; Britton, G.J.; Miller, Haley; Magri, Giuliana; Tomalin, L.; Stapylton, M.; Canales-Herrerias, P.; Sominskaia, M.; Guzman, Mauricio; Pybus, Marc; Tejedor Vaquero, Sonia; Radigan, L.; Tachó-Piñot, Roser; Nalda, A.M.; Prat, M.G.; Martínez Gallo, Mónica; Dieli-Crimi, Romina; Clemente, J.C.; Mehandru, S.; Suarez-Farinas, M.; Faith, J.J.; Cunningham-Rundles, C.; Cerutti, Andrea; Universitat Autònoma de Barcelona |
| Publication Year: |
2025 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Subject Terms: |
B cells; Germ-free mice; Gut bacteria; Gut microbes; Gut microbiota; IgA deficiencies; Immune activation; Immunoglobulin G; Overexpressions; Programmed cell deaths; Animals; B-Lymphocytes; Gastrointestinal Microbiome; Humans; Immunoglobulin A; Mice; Pneumococcal Vaccines; Programmed Cell Death 1 Receptor; Streptococcus pneumoniae; T-Lymphocytes |
| Description: |
The gut microbiota enhances systemic immunoglobulin G (IgG) responses to vaccines, but it is unknown whether this effect involves IgA, which coats intestinal microbes. That IgA may amplify postimmune IgG production is suggested by the impaired IgG response to pneumococcal vaccines in some IgA-deficient patients. Here, we found that antipneumococcal but not total IgG production was impaired in mice with IgA deficiency. The positive effect of gut IgA on antipneumococcal IgG responses started very early in life and could implicate gut bacteria, as these responses were attenuated in germ-free mice recolonized with gut microbes from IgA-deficient donors. IgA could exert this effect by constraining the systemic translocation of gut antigens, which was associated with chronic immune activation, including T cell overexpression of programmed cell death protein 1 (PD-1). This inhibitory receptor may attenuate antipneumococcal IgG production by causing B cell hyporesponsiveness, which improved upon anti-PD-1 treatment. Thus, gut IgA functionally interacts with systemic IgG to enhance antipneumococcal vaccine responses. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISBN: |
978-2-01-809389-2; 2-01-809389-4 |
| ISSN: |
23752548 |
| Relation: |
Agencia Estatal de Investigación RTI2018-093894-B-I00; Science advances; Vol. 11 Núm. 7 (14 2025), p. eado9455; https://ddd.uab.cat/record/321083; urn:10.1126/sciadv.ado9455; urn:oai:ddd.uab.cat:321083; urn:scopus_id:85218355778; urn:articleid:23752548v11n7aeado9455; urn:oai:pubmedcentral.nih.gov:11817949; urn:pmid:39937896; urn:pmcid:PMC11817949 |
| Availability: |
https://ddd.uab.cat/record/321083 |
| Rights: |
open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. ; https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.9844E5EB |
| Database: |
BASE |