Cited by 399Autophagy in Disease and TherapyCellular transport and secretionImmune Response and Inflammation

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Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine

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Bel, Shai, Pendse, Mihir, Wang, Yuhao, Li, Yun, Ruhn, Kelly A., Hassell, Brian, Leal, Tess, Winter, Sebastian E., Xavier, Ramnik J., Hooper, Lora V.·2017·Science

DOI 10.1126/science.aal4677PMC PMC5702267

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Abstract

Foiling bad bugs' sneaky tricks: Intestinal pathogens can invade host cells and disrupt critical cellular functions, including secretion. Secretion is necessary for the delivery of antimicrobial proteins that kill pathogenic bacteria. Bel et al. show that when intestinal epithelial cells sense an invading bacterial pathogen, they “reroute” the antimicrobial protein lysozyme through an alternative autophagy-based secretion pathway (see the Perspective by Kaser and Blumberg). This ensures lysozyme delivery to the gut lumen, which protects against further bacterial invasion. Secretory autophagy was triggered by endoplasmic reticulum stress and required signals from type 3 innate lymphoid cells. Thus, the innate immune response to gut pathogens co-opts autophagy in intestinal immune defense. Science , this issue p. 1047 ; see also p. 976

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Additional file 9 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
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Additional file 7 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
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Additional file 2 of Gut bacterial metabolites modulate endoplasmic reticulum stress
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Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218534
Additional file 3 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218543
Additional file 1 of Integration of multi-omics data reveals cis-regulatory variants that are associated with phenotypic differentiation of eastern from western pigs
Liu, Y., Fu, Y., Yang, Y., Yi, G., Lian, J., Xie, B., Yao, Y., Chen, M., Niu, Y., Liu, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21117428
Additional file 12 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218531
Additional file 5 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218558
Additional file 3 of Integration of multi-omics data reveals cis-regulatory variants that are associated with phenotypic differentiation of eastern from western pigs
Liu, Y., Fu, Y., Yang, Y., Yi, G., Lian, J., Xie, B., Yao, Y., Chen, M., Niu, Y., Liu, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21117440
Additional file 8 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218576
Additional file 2 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218537
Additional file 4 of Gut bacterial metabolites modulate endoplasmic reticulum stress
Ke, X., You, K., Pichaud, M., Haiser, H. J., Graham, D. B., Vlamakis, H. C., Porter, J. A., & Xavier, R. J. (2021) · Figshare · doi:10.6084/m9.figshare.16821527
Self-citation
Additional file 6 of Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization
Li, Z., Fu, W.-J., Chen, X.-Q., Wang, S., Deng, R.-S., Tang, X.-P., Yang, K.-D., Niu, Q., Zhou, H., Li, Q.-R., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19218564
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Authors: Bel, S., Pendse, M., Wang, Y., Li, Y., Ruhn, K. A., Hassell, B., Leal, T., Winter, S. E., Xavier, R. J., & Hooper, L. V.
Affiliations: The University of Texas Southwestern Medical Center (US)
Broad Institute (US)
Howard Hughes Medical Institute (US)
Corresponding author: Hooper, Lora V.
ORCID: Bel, Shai
Pendse, Mihir
Wang, Yuhao
Li, Yun
Ruhn, Kelly A.
Hassell, Brian
Leal, Tess
Winter, Sebastian E.
Xavier, Ramnik J.
Hooper, Lora V.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2017-09-08
Volume: 357
Issue: 6355
Pages: 1047-1052
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aal4677
PMC: PMC5702267
OpenAlex: W2740220090
Cited by: 396
References: 27
Citations by year: 2026: 28 · 2025: 46 · 2024: 42 · 2023: 43 · 2022: 70 · 2021: 41 · 2020: 37 · 2019: 46 · 2018: 30 · 2017: 13
FWCI: 27.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (award310630, DK070855, award339066, AI118807, award339067, AI128151)
Howard Hughes Medical Institute (award310633, N/A)
Welch Foundation (award310632, I-1874, award339068, I-1858)
Burroughs Wellcome Foundation (award310631, 1007035)
Gruss-Lipper Foundation (award310634, N/A)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: Paneth cells, lysozyme secretion, secretory autophagy, intestinal epithelial cells, bacterial intestinal infections, endoplasmic reticulum stress, ILC3, antimicrobial proteins, innate immune response
MeSH terms: Autophagy-Related Proteins, Animals, Autophagy, Carrier Proteins, Crohn Disease, Mice, Inbred C57BL, Microtubule-Associated Proteins, Muramidase, Mutation, Salmonella Infections, Salmonella enterica, Paneth Cells, Mice, Endoplasmic Reticulum Stress

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Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine

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