Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption

doi:10.7554/eLife.76729

	Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption
	Zhang, Chenlu1,2 ; Hu, Zehan 3,4; Lone, Abdul G.1; Artami, Methinee 1; Edwards, Marshall 1; Zouboulis, Christos C.5,6; Stein, Maggie 1; Harris-Tryon, Tamia A.1,3; Kim, Brian S.
	2022-03
发表期刊	ELIFE (IF:6.4[JCR-2023],7.2[5-Year])
ISSN	2050-084X
卷号	11
发表状态	已发表
DOI	10.7554/eLife.76729
摘要	Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here, we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Colonization of germ-free mice was insufficient to trigger increased SPRR expression in mouse skin, but LPS injected into mouse skin stimulated increased expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through activation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa, and skin commensals. Thus, Sprr1a(-/-);Sprr2a(-/-) mice are more susceptible to MRSA and P. aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.
关键词	skin innate immunity antimicrobial proteins LPS sebaceous glands Human Mouse Other
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS类目	Biology
WOS记录号	WOS:000770854300001
出版者	eLIFE SCIENCES PUBL LTD
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/162918
专题	生命科学与技术学院_PI研究组_张晨璐组
通讯作者	Zhang, Chenlu; Harris-Tryon, Tamia A.
作者单位	1.Univ Texas Southwestern Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA 4.Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Joint Int Res Lab Metab & Dev Sci, Sch Life Sci & Biotechnol, Shanghai, Peoples R China 5.Brandenburg Med Sch Theodore Fontane, Dept Dermatol Venereol Allergol & Immunol, Dessau Med Ctr, Dessau, Germany 6.Fac Hlth Sci Brandenburg, Dessau, Germany
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Chenlu,Hu, Zehan,Lone, Abdul G.,et al. Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption[J]. ELIFE,2022,11.
APA	Zhang, Chenlu.,Hu, Zehan.,Lone, Abdul G..,Artami, Methinee.,Edwards, Marshall.,...&Kim, Brian S..(2022).Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption.ELIFE,11.
MLA	Zhang, Chenlu,et al."Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption".ELIFE 11(2022).