Enteric defensins are essential regulators of intestinal microbial ecology

Nita H. Salzman; Kuiechun Hung; Dipica Haribhai; Hiutung Chu; Jenny Karlsson-Sjoeberg; Elad Amir; Paul Teggatz; Melissa Barman; Michael Hayward; Daniel Eastwood; Maaike Stoel; Yanjiao Zhou; Erica Sodergren; George M. Weinstock; Charles L. Bevins; Calvin B. Williams; Nicolaas A. Bos

doi:10.1038/ni.1825

Enteric defensins are essential regulators of intestinal microbial ecology

Nita H. Salzman^*, Kuiechun Hung, Dipica Haribhai, Hiutung Chu, Jenny Karlsson-Sjoeberg, Elad Amir, Paul Teggatz, Melissa Barman, Michael Hayward, Daniel Eastwood, Maaike Stoel, Yanjiao Zhou, Erica Sodergren, George M. Weinstock, Charles L. Bevins, Calvin B. Williams, Nicolaas A. Bos

^*Corresponding author for this work

Translational Immunology Groningen (TRIGR)

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

953 Citations (Scopus)

Abstract

Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell alpha-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if alpha-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human alpha-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse alpha-defensins. In these complementary models, we detected significant alpha-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to alpha-defensins in regulating the makeup of the commensal microbiota.

Original language	English
Pages (from-to)	76-U1
Number of pages	8
Journal	Nature Immunology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/ni.1825
Publication status	Published - Jan-2010

Keywords

SEGMENTED FILAMENTOUS BACTERIA
DISTAL GUT MICROBIOME
PANETH CELL
ANTIMICROBIAL PEPTIDES
IMMUNE-RESPONSE
INNATE IMMUNITY
MOUSE
DISEASE
MICE
COLONIZATION

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Salzman, N. H., Hung, K., Haribhai, D., Chu, H., Karlsson-Sjoeberg, J., Amir, E., Teggatz, P., Barman, M., Hayward, M., Eastwood, D., Stoel, M., Zhou, Y., Sodergren, E., Weinstock, G. M., Bevins, C. L., Williams, C. B., & Bos, N. A. (2010). Enteric defensins are essential regulators of intestinal microbial ecology. Nature Immunology, 11(1), 76-U1. https://doi.org/10.1038/ni.1825

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abstract = "Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell alpha-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if alpha-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human alpha-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse alpha-defensins. In these complementary models, we detected significant alpha-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to alpha-defensins in regulating the makeup of the commensal microbiota.",

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AU - Salzman, Nita H.

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AU - Karlsson-Sjoeberg, Jenny

AU - Amir, Elad

AU - Teggatz, Paul

AU - Barman, Melissa

AU - Hayward, Michael

AU - Eastwood, Daniel

AU - Stoel, Maaike

AU - Zhou, Yanjiao

AU - Sodergren, Erica

AU - Weinstock, George M.

AU - Bevins, Charles L.

AU - Williams, Calvin B.

AU - Bos, Nicolaas A.

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AB - Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell alpha-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if alpha-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human alpha-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse alpha-defensins. In these complementary models, we detected significant alpha-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to alpha-defensins in regulating the makeup of the commensal microbiota.

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KW - PANETH CELL

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KW - IMMUNE-RESPONSE

KW - INNATE IMMUNITY

KW - MOUSE

KW - DISEASE

KW - MICE

KW - COLONIZATION

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DO - 10.1038/ni.1825

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VL - 11

SP - 76-U1

JO - Nature Immunology

JF - Nature Immunology

IS - 1

ER -

Enteric defensins are essential regulators of intestinal microbial ecology

Abstract

Keywords

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