Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets

Hiutung Chu; Marzena Pazgier; Grace Jung; Sean Paul Nuccio; Patricia A. Castillo; Maarten F. De Jong; Maria G. Winter; Sebastian E. Winter; Jan Wehkamp; Bo Shen; Nita H. Salzman; Mark A. Underwood; Renee M. Tsolis; Glenn M. Young; Wuyuan Lu; Robert I. Lehrer; Andreas J. Bäumler; Charles L. Bevins

doi:10.1126/science.1218831

Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets

Hiutung Chu, Marzena Pazgier, Grace Jung, Sean Paul Nuccio, Patricia A. Castillo, Maarten F. De Jong, Maria G. Winter, Sebastian E. Winter, Jan Wehkamp, Bo Shen, Nita H. Salzman, Mark A. Underwood, Renee M. Tsolis, Glenn M. Young, Wuyuan Lu, Robert I. Lehrer, Andreas J. Bäumler, Charles L. Bevins

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

306 Scopus citations

Abstract

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

Original language	English (US)
Pages (from-to)	477-481
Number of pages	5
Journal	Science
Volume	337
Issue number	6093
DOIs	https://doi.org/10.1126/science.1218831
State	Published - Jul 27 2012

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Chu, H., Pazgier, M., Jung, G., Nuccio, S. P., Castillo, P. A., De Jong, M. F., Winter, M. G., Winter, S. E., Wehkamp, J., Shen, B., Salzman, N. H., Underwood, M. A., Tsolis, R. M., Young, G. M., Lu, W., Lehrer, R. I., Bäumler, A. J., & Bevins, C. L. (2012). Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science, 337(6093), 477-481. https://doi.org/10.1126/science.1218831

Chu, H, Pazgier, M, Jung, G, Nuccio, SP, Castillo, PA, De Jong, MF, Winter, MG, Winter, SE, Wehkamp, J, Shen, B, Salzman, NH, Underwood, MA, Tsolis, RM, Young, GM, Lu, W, Lehrer, RI, Bäumler, AJ & Bevins, CL 2012, 'Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets', Science, vol. 337, no. 6093, pp. 477-481. https://doi.org/10.1126/science.1218831

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title = "Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets",

abstract = "Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.",

author = "Hiutung Chu and Marzena Pazgier and Grace Jung and Nuccio, {Sean Paul} and Castillo, {Patricia A.} and {De Jong}, {Maarten F.} and Winter, {Maria G.} and Winter, {Sebastian E.} and Jan Wehkamp and Bo Shen and Salzman, {Nita H.} and Underwood, {Mark A.} and Tsolis, {Renee M.} and Young, {Glenn M.} and Wuyuan Lu and Lehrer, {Robert I.} and B{\"a}umler, {Andreas J.} and Bevins, {Charles L.}",

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AU - De Jong, Maarten F.

AU - Winter, Maria G.

AU - Winter, Sebastian E.

AU - Wehkamp, Jan

AU - Shen, Bo

AU - Salzman, Nita H.

AU - Underwood, Mark A.

AU - Tsolis, Renee M.

AU - Young, Glenn M.

AU - Lu, Wuyuan

AU - Lehrer, Robert I.

AU - Bäumler, Andreas J.

AU - Bevins, Charles L.

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AB - Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

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Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets

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