Intelectin-2 is a broad-spectrum antimicrobial lectin
Mammals regulate the localization, composition, and activity of their native microbiota at colonization sites. Lectins residing at these sites influence microbial populations, but their functional roles are often unclear. Intelectins are found in chordates at mucosal barriers, but their functions are not well characterized. In this study, we find that mouse intelectin-2 (mItln2) and human intelectin-2 (hItln2) engage and crosslink mucins via carbohydrate recognition. Moreover, both lectins recognize microbes within native microbial communities, including gram-positive and gram-negative isolates from the respiratory and gastrointestinal tracts. This ability to engage mammalian and microbial glycans arises from calcium-coordinated binding of carbohydrate residues within mucus and microbial surfaces. Microbes, but not human cells, bound by mItln2 or hItln2, suffer a loss of viability. These findings underscore the crucial antimicrobial role of mammalian intelectin-2 in mucosal defense, where it plays offensive (microbial killing) and defensive (mucus crosslinking) roles in regulating microbial colonization.
Authors
- Charles Bevins (ORCID: https://orcid.org/0000-0003-2725-2622)
- Sheila Johnson (ORCID: https://orcid.org/0000-0001-5062-7934)
- Eric B. Nonnecke (ORCID: https://orcid.org/0000-0001-5345-2009)
- Miri Krupkin (ORCID: https://orcid.org/0000-0002-5917-0894)
- Rajeev Chorghade (ORCID: https://orcid.org/0000-0001-7162-1419)
- Chariesse Ellis
- Amanda Dugan (ORCID: https://orcid.org/0000-0003-3135-8155)
- Gleb Pishchany (ORCID: https://orcid.org/0000-0001-9303-010X)
- Jenny Yao (ORCID: https://orcid.org/0000-0003-3405-9943)
- Sunhee Bae (ORCID: https://orcid.org/0000-0002-8913-9476)
- Deepsing Syangtan (ORCID: https://orcid.org/0000-0001-5245-4782)
- Catherine Dhennezel (ORCID: https://orcid.org/0000-0003-3273-7165)
- Dallis Sergio (ORCID: https://orcid.org/0000-0001-9290-7088)
- Amanda L. Peiffer (ORCID: https://orcid.org/0000-0001-8113-9458)
- Gerardo Cárcamo-Oyarce (ORCID: https://orcid.org/0009-0004-4827-4892)
- Soumi Ghosh
- Jill W. Alty
- Hera Vlamakis
- Laura L. Kiessling
- Katharina Ribbeck
- Carolyn E. Barnes
- Ramnik J. Xavier
- Jessica Ille-Bunn
Institutions
- Broad Institute (US)
- University of Wisconsin–Madison (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Massachusetts Institute of Technology (US)
- University of California, Davis (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-13
- DOI
- https://doi.org/10.1038/s41467-025-67099-4
- Primary Topic
- Invertebrate Immune Response Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- Common Fund