Format

Send to

Choose Destination
Sci Immunol. 2020 Feb 7;5(44). pii: eaay3254. doi: 10.1126/sciimmunol.aay3254.

Specialization of mucosal immunoglobulins in pathogen control and microbiota homeostasis occurred early in vertebrate evolution.

Author information

1
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
3
Faculty of Marine Science and Technology, Fukui Prefectural University, Obama, Fukui 917-0003, Japan.
4
Center for Evolutionary and Theoretical Immunology (CETI), Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
5
Center for Evolutionary and Theoretical Immunology (CETI), Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA. sunyer@vet.upenn.edu isalinas@unm.edu.
6
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. sunyer@vet.upenn.edu isalinas@unm.edu.

Abstract

Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect mucosal surfaces from pathogens or to maintain microbiome homeostasis. To address this central question, we used a primitive vertebrate species (rainbow trout) in which we temporarily depleted its mucosal Ig (sIgT). Fish devoid of sIgT became highly susceptible to a mucosal parasite and failed to develop compensatory IgM responses against it. IgT depletion also induced a profound dysbiosis marked by the loss of sIgT-coated beneficial taxa, expansion of pathobionts, tissue damage, and inflammation. Restitution of sIgT levels in IgT-depleted fish led to a reversal of microbial translocation and tissue damage, as well as to restoration of microbiome homeostasis. Our findings indicate that specialization of sIgs in pathogen and microbiota control occurred concurrently early in evolution, thus revealing primordially conserved principles under which primitive and modern sIgs operate in the control of microbes at mucosal surfaces.

PMID:
32034088
DOI:
10.1126/sciimmunol.aay3254

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center