Intelectin-2 is a broad-spectrum antimicrobial lectin

Amanda E. Dugan; Deepsing Syangtan; Eric B. Nonnecke; Rajeev S. Chorghade; Amanda L. Peiffer; Jenny J. Yao; Jessica Ille-Bunn; Dallis Sergio; Gleb Pishchany; Catherine Dhennezel; Hera Vlamakis; Sunhee Bae; Sheila Johnson; Chariesse Ellis; Soumi Ghosh; Jill W. Alty; Carolyn E. Barnes; Miri Krupkin; Gerardo Cárcamo-Oyarce; Katharina Ribbeck; Ramnik J. Xavier; Charles L. Bevins; Laura L. Kiessling

doi:10.1038/s41467-025-67099-4

Intelectin-2 is a broad-spectrum antimicrobial lectin

Amanda E. Dugan
, Deepsing Syangtan
, Eric B. Nonnecke
, Rajeev S. Chorghade
, Amanda L. Peiffer
, Jenny J. Yao
, Jessica Ille-Bunn
, Dallis Sergio
, Gleb Pishchany
, Catherine Dhennezel
, Hera Vlamakis
, Sunhee Bae
, Sheila Johnson
, Chariesse Ellis
, Soumi Ghosh
, Jill W. Alty
, Carolyn E. Barnes
, Miri Krupkin
, Gerardo Cárcamo-Oyarce
, Katharina Ribbeck

Ramnik J. Xavier, Charles L. Bevins, Laura L. Kiessling

Chemistry

Massachusetts Institute of Technology
University of California at Davis
Broad Institute
University of Wisconsin-Madison
Massachusetts General Hospital

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	231
Journal	Nature Communications
Volume	17
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-67099-4
State	Published - Dec 2026

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Dugan, A. E., Syangtan, D., Nonnecke, E. B., Chorghade, R. S., Peiffer, A. L., Yao, J. J., Ille-Bunn, J., Sergio, D., Pishchany, G., Dhennezel, C., Vlamakis, H., Bae, S., Johnson, S., Ellis, C., Ghosh, S., Alty, J. W., Barnes, C. E., Krupkin, M., Cárcamo-Oyarce, G., ... Kiessling, L. L. (2026). Intelectin-2 is a broad-spectrum antimicrobial lectin. Nature Communications, 17(1), Article 231. https://doi.org/10.1038/s41467-025-67099-4

@article{b74d9a9328124a55a674432f1324624e,

title = "Intelectin-2 is a broad-spectrum antimicrobial lectin",

abstract = "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.",

author = "Dugan, \{Amanda E.\} and Deepsing Syangtan and Nonnecke, \{Eric B.\} and Chorghade, \{Rajeev S.\} and Peiffer, \{Amanda L.\} and Yao, \{Jenny J.\} and Jessica Ille-Bunn and Dallis Sergio and Gleb Pishchany and Catherine Dhennezel and Hera Vlamakis and Sunhee Bae and Sheila Johnson and Chariesse Ellis and Soumi Ghosh and Alty, \{Jill W.\} and Barnes, \{Carolyn E.\} and Miri Krupkin and Gerardo C{\'a}rcamo-Oyarce and Katharina Ribbeck and Xavier, \{Ramnik J.\} and Bevins, \{Charles L.\} and Kiessling, \{Laura L.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026.",

year = "2026",

month = dec,

doi = "10.1038/s41467-025-67099-4",

language = "English",

volume = "17",

journal = "Nature Communications",

issn = "2041-1723",

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Dugan, AE, Syangtan, D, Nonnecke, EB, Chorghade, RS, Peiffer, AL, Yao, JJ, Ille-Bunn, J, Sergio, D, Pishchany, G, Dhennezel, C, Vlamakis, H, Bae, S, Johnson, S, Ellis, C, Ghosh, S, Alty, JW, Barnes, CE, Krupkin, M, Cárcamo-Oyarce, G, Ribbeck, K, Xavier, RJ, Bevins, CL & Kiessling, LL 2026, 'Intelectin-2 is a broad-spectrum antimicrobial lectin', Nature Communications, vol. 17, no. 1, 231. https://doi.org/10.1038/s41467-025-67099-4

TY - JOUR

T1 - Intelectin-2 is a broad-spectrum antimicrobial lectin

AU - Dugan, Amanda E.

AU - Syangtan, Deepsing

AU - Nonnecke, Eric B.

AU - Chorghade, Rajeev S.

AU - Peiffer, Amanda L.

AU - Yao, Jenny J.

AU - Ille-Bunn, Jessica

AU - Sergio, Dallis

AU - Pishchany, Gleb

AU - Dhennezel, Catherine

AU - Vlamakis, Hera

AU - Bae, Sunhee

AU - Johnson, Sheila

AU - Ellis, Chariesse

AU - Ghosh, Soumi

AU - Alty, Jill W.

AU - Barnes, Carolyn E.

AU - Krupkin, Miri

AU - Cárcamo-Oyarce, Gerardo

AU - Ribbeck, Katharina

AU - Xavier, Ramnik J.

AU - Bevins, Charles L.

AU - Kiessling, Laura L.

PY - 2026/12

Y1 - 2026/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105027348291

U2 - 10.1038/s41467-025-67099-4

DO - 10.1038/s41467-025-67099-4

M3 - Article

C2 - 41530121

AN - SCOPUS:105027348291

SN - 2041-1723

VL - 17

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 231

ER -

Intelectin-2 is a broad-spectrum antimicrobial lectin

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