Gut complement induced by the microbiota combats pathogens and spares commensals

Meng Wu; Wen Zheng; Xinyang Song; Bin Bao; Yuanyou Wang; Deepshika Ramanan; Daping Yang; Rui Liu; John C. Macbeth; Elyza A. Do; Warrison A. Andrade; Tiandi Yang; Hyoung Soo Cho; Francesca S. Gazzaniga; Marit Ilves; Daniela Coronado; Charlotte Thompson; Saiyu Hang; Isaac M. Chiu; Jeffrey R. Moffitt; Ansel Hsiao; John J. Mekalanos; Christophe Benoist; Dennis L. Kasper

doi:10.1016/j.cell.2023.12.036

Gut complement induced by the microbiota combats pathogens and spares commensals

Meng Wu, Wen Zheng, Xinyang Song, Bin Bao, Yuanyou Wang, Deepshika Ramanan, Daping Yang, Rui Liu, John C. Macbeth, Elyza A. Do, Warrison A. Andrade, Tiandi Yang, Hyoung Soo Cho, Francesca S. Gazzaniga, Marit Ilves, Daniela Coronado, Charlotte Thompson, Saiyu Hang, Isaac M. Chiu, Jeffrey R. MoffittAnsel Hsiao, John J. Mekalanos, Christophe Benoist, Dennis L. Kasper

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

11 Scopus citations

Abstract

Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.

Original language	English
Pages (from-to)	897-913.e18
Journal	Cell
Volume	187
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2023.12.036
State	Published - Feb 15 2024

Keywords

complement C3
gut complement system
innate immunity
isolated lymphoid follicles
microbiome
microbiota
stromal cells

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10.1016/j.cell.2023.12.036

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Wu, M., Zheng, W., Song, X., Bao, B., Wang, Y., Ramanan, D., Yang, D., Liu, R., Macbeth, J. C., Do, E. A., Andrade, W. A., Yang, T., Cho, H. S., Gazzaniga, F. S., Ilves, M., Coronado, D., Thompson, C., Hang, S., Chiu, I. M., ... Kasper, D. L. (2024). Gut complement induced by the microbiota combats pathogens and spares commensals. Cell, 187(4), 897-913.e18. https://doi.org/10.1016/j.cell.2023.12.036

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title = "Gut complement induced by the microbiota combats pathogens and spares commensals",

abstract = "Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.",

keywords = "complement C3, gut complement system, innate immunity, isolated lymphoid follicles, microbiome, microbiota, stromal cells",

author = "Meng Wu and Wen Zheng and Xinyang Song and Bin Bao and Yuanyou Wang and Deepshika Ramanan and Daping Yang and Rui Liu and Macbeth, {John C.} and Do, {Elyza A.} and Andrade, {Warrison A.} and Tiandi Yang and Cho, {Hyoung Soo} and Gazzaniga, {Francesca S.} and Marit Ilves and Daniela Coronado and Charlotte Thompson and Saiyu Hang and Chiu, {Isaac M.} and Moffitt, {Jeffrey R.} and Ansel Hsiao and Mekalanos, {John J.} and Christophe Benoist and Kasper, {Dennis L.}",

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier Inc.",

year = "2024",

month = feb,

day = "15",

doi = "10.1016/j.cell.2023.12.036",

language = "English",

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Wu, M, Zheng, W, Song, X, Bao, B, Wang, Y, Ramanan, D, Yang, D, Liu, R, Macbeth, JC, Do, EA, Andrade, WA, Yang, T, Cho, HS, Gazzaniga, FS, Ilves, M, Coronado, D, Thompson, C, Hang, S, Chiu, IM, Moffitt, JR, Hsiao, A, Mekalanos, JJ, Benoist, C & Kasper, DL 2024, 'Gut complement induced by the microbiota combats pathogens and spares commensals', Cell, vol. 187, no. 4, pp. 897-913.e18. https://doi.org/10.1016/j.cell.2023.12.036

TY - JOUR

T1 - Gut complement induced by the microbiota combats pathogens and spares commensals

AU - Wu, Meng

AU - Zheng, Wen

AU - Song, Xinyang

AU - Bao, Bin

AU - Wang, Yuanyou

AU - Ramanan, Deepshika

AU - Yang, Daping

AU - Liu, Rui

AU - Macbeth, John C.

AU - Do, Elyza A.

AU - Andrade, Warrison A.

AU - Yang, Tiandi

AU - Cho, Hyoung Soo

AU - Gazzaniga, Francesca S.

AU - Ilves, Marit

AU - Coronado, Daniela

AU - Thompson, Charlotte

AU - Hang, Saiyu

AU - Chiu, Isaac M.

AU - Moffitt, Jeffrey R.

AU - Hsiao, Ansel

AU - Mekalanos, John J.

AU - Benoist, Christophe

AU - Kasper, Dennis L.

PY - 2024/2/15

Y1 - 2024/2/15

N2 - Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.

AB - Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.

KW - complement C3

KW - gut complement system

KW - innate immunity

KW - isolated lymphoid follicles

KW - microbiome

KW - microbiota

KW - stromal cells

UR - http://www.scopus.com/inward/record.url?scp=85184773289&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2023.12.036

DO - 10.1016/j.cell.2023.12.036

M3 - Article

C2 - 38280374

AN - SCOPUS:85184773289

SN - 0092-8674

VL - 187

SP - 897-913.e18

JO - Cell

JF - Cell

IS - 4

ER -

Gut complement induced by the microbiota combats pathogens and spares commensals

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Keywords

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