Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection

Zehan Hu; Chenlu Zhang; Luis Sifuentes-Dominguez; Christina M. Zarek; Daniel C. Propheter; Zheng Kuang; Yuhao Wang; Mihir Pendse; Kelly A. Ruhn; Brian Hassell; Cassie L. Behrendt; Bo Zhang; Prithvi Raj; Tamia A. Harris-Tryon; Tiffany A. Reese; Lora V. Hooper

doi:10.1126/science.abe6723

Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection

Zehan Hu, Chenlu Zhang, Luis Sifuentes-Dominguez, Christina M. Zarek, Daniel C. Propheter, Zheng Kuang, Yuhao Wang, Mihir Pendse, Kelly A. Ruhn, Brian Hassell, Cassie L. Behrendt, Bo Zhang, Prithvi Raj, Tamia A. Harris-Tryon, Tiffany A. Reese, Lora V. Hooper

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Abstract

A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.

Original language	English (US)
Article number	eabe6723
Journal	Science
Volume	374
Issue number	6568
DOIs	https://doi.org/10.1126/science.abe6723
State	Published - Nov 5 2021

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Hu, Z., Zhang, C., Sifuentes-Dominguez, L., Zarek, C. M., Propheter, D. C., Kuang, Z., Wang, Y., Pendse, M., Ruhn, K. A., Hassell, B., Behrendt, C. L., Zhang, B., Raj, P., Harris-Tryon, T. A., Reese, T. A., & Hooper, L. V. (2021). Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection. Science, 374(6568), Article eabe6723. https://doi.org/10.1126/science.abe6723

Hu, Z, Zhang, C, Sifuentes-Dominguez, L, Zarek, CM, Propheter, DC, Kuang, Z, Wang, Y, Pendse, M, Ruhn, KA, Hassell, B, Behrendt, CL, Zhang, B, Raj, P , Harris-Tryon, TA , Reese, TA & Hooper, LV 2021, 'Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection', Science, vol. 374, no. 6568, eabe6723. https://doi.org/10.1126/science.abe6723

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title = "Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection",

abstract = "A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.",

author = "Zehan Hu and Chenlu Zhang and Luis Sifuentes-Dominguez and Zarek, {Christina M.} and Propheter, {Daniel C.} and Zheng Kuang and Yuhao Wang and Mihir Pendse and Ruhn, {Kelly A.} and Brian Hassell and Behrendt, {Cassie L.} and Bo Zhang and Prithvi Raj and Harris-Tryon, {Tamia A.} and Reese, {Tiffany A.} and Hooper, {Lora V.}",

year = "2021",

month = nov,

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doi = "10.1126/science.abe6723",

language = "English (US)",

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AU - Zarek, Christina M.

AU - Propheter, Daniel C.

AU - Kuang, Zheng

AU - Wang, Yuhao

AU - Pendse, Mihir

AU - Ruhn, Kelly A.

AU - Hassell, Brian

AU - Behrendt, Cassie L.

AU - Zhang, Bo

AU - Raj, Prithvi

AU - Harris-Tryon, Tamia A.

AU - Reese, Tiffany A.

AU - Hooper, Lora V.

PY - 2021/11/5

Y1 - 2021/11/5

N2 - A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.

AB - A diverse group of antimicrobial proteins (AMPs) helps protect the mammalian intestine from varied microbial challenges. We show that small proline-rich protein 2A (SPRR2A) is an intestinal antibacterial protein that is phylogenetically unrelated to previously discovered mammalian AMPs. In this study, SPRR2A was expressed in Paneth cells and goblet cells and selectively killed Gram-positive bacteria by disrupting their membranes. SPRR2A shaped intestinal microbiota composition, restricted bacterial association with the intestinal surface, and protected against Listeria monocytogenes infection. SPRR2A differed from other intestinal AMPs in that it was induced by type 2 cytokines produced during helminth infection. Moreover, SPRR2A protected against helminth-induced bacterial invasion of intestinal tissue. Thus, SPRR2A is a distinctive AMP triggered by type 2 immunity that protects the intestinal barrier during helminth infection.

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Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection

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