Collectin 11 has a pivotal role in host defense against kidney and bladder infection in mice

作者全名："Wu, Kun-Yi; Cao, Bo; Chen, Wan-Bing; Wu, Weiju; Zhao, Shujuan; Min, Xiao-Yun; Yang, Jurong; Han, Jin; Dong, Xia; Wang, Na; Wu, Yi; Garred, Peter; Sacks, Steven H.; Zhou, Wuding; Li, Ke"

作者地址："[Wu, Kun-Yi; Cao, Bo; Chen, Wan-Bing; Zhao, Shujuan; Min, Xiao-Yun; Wang, Na; Li, Ke] Xi An Jiao Tong Univ, Affiliated Hosp 2, Core Res Lab, Xian, Peoples R China; [Wu, Weiju; Sacks, Steven H.; Zhou, Wuding] Kings Coll London, Fac Life Sci & Med, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London, England; [Yang, Jurong] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 3, Chongqing, Peoples R China; [Han, Jin] Xi An Jiao Tong Univ, Dept Nephrol, Affiliated Hosp 2, Xian, Peoples R China; [Dong, Xia] Sun Yat sen Univ, Affiliated Hosp 1, Dept Ophthalmol, Guangzhou, Guangdong, Peoples R China; [Wu, Yi] Xi An Jiao Tong Univ, Sch Basic Med Sci, MOE, Key Lab Environm & Genes Related Dis, Xian, Peoples R China; [Garred, Peter] Rigshosp, Lab Mol Med, Rigshospitalet, Copenhagen, Denmark; [Garred, Peter] Univ Copenhagen, Copenhagen, Denmark; [Li, Ke] Xi An Jiao Tong Univ, Affiliated Hosp 2, Sch Med, Core Res Lab, Xian 710004, Peoples R China; [Zhou, Wuding] Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London SE1 9RT, England"

通信作者："Li, K (通讯作者)，Xi An Jiao Tong Univ, Affiliated Hosp 2, Sch Med, Core Res Lab, Xian 710004, Peoples R China.; Zhou, WD (通讯作者)，Kings Coll London, Guys Hosp, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London SE1 9RT, England."

来源：KIDNEY INTERNATIONAL

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001189358800001

JCR分区：Q1

影响因子：19.6

年份：2024

卷号：105

期号：3

开始页：524

结束页：539

文献类型：Article

关键词：collectin 11; cystitis; pyelonephritis; urinary tract infections; uropathogenic E. coli

摘要："The urinary tract is constantly exposed to microorganisms. Host defense mechanisms in protection from microbial colonization and development of urinary tract infections require better understanding to control kidney infection. Here we report that the lectin collectin 11 (CL-11), particularly kidney produced, has a pivotal role in host defense against uropathogen infection. CL-11 was found in mouse urine under normal and pathological conditions. Mice with global gene ablation of Colec11 had increased susceptibility to and severity of kidney and to an extent, bladder infection. Mice with kidney-specific Colec11 ablation exhibited a similar disease phenotype to that observed in global Colec11 deficient mice, indicating the importance of kidney produced CL-11 for protection against kidney and bladder infection. Conversely, intravesical or systemic administration of recombinant CL11 reduced susceptibility to and severity of kidney and bladder infection. Mechanism analysis revealed that CL-11 can mediate several key innate defense mechanisms (agglutination, anti- adhesion, opsonophagocytosis), and limit local inflammatory responses to pathogens. Furthermore, CL-11-mediated innate defense mechanisms can act on clinically relevant microorganisms including multiple antibiotic resistant strains. CL-11 was detectable in eight of 24 urine samples from patients with urinary tract infections but not detectable in urine samples from ten healthy individuals. Thus, our findings demonstrate that CL-11 is a key factor of host defense mechanisms in kidney and bladder infection with therapeutic potential for human application."

基金机构："National Natural Science Foundation of China [NSFC 81970596]; Natural Science Foundation of Shaanxi Province of China [2021JM-287, 2023-ZDLSF-10]; Medical Research Council UK [MR/L020254/1, MR/J006742/1, MR/M012263/1]"

基金资助正文："The authors thank Mutant Mouse Resource and Research Centers (University of California, Davis, Davis, CA) for providing Colec11<SUP>-/-</SUP> mice. This work was supported by the National Natural Science Foundation of China (NSFC 81970596 to KL) , the Natural Science Foundation of Shaanxi Province of China (2021JM-287 to XYM and KL; 2023-ZDLSF-10 to YW and KL) , and the Medical Research Council UK (MR/L020254/1 to WZ and SS; MR/J006742/1 to SS; MR/M012263/1 to SS and WZ) ."