The chemerin-CMKLR1 axis in keratinocytes impairs innate host defense against cutaneous <i>Staphylococcus aureus</i> infection

作者全名："Chen, Yu; Song, Yan; Wang, Zhe; Lai, Yangfan; Yin, Wei; Cai, Qian; Han, Miaomiao; Cai, Yiheng; Xue, Yushan; Chen, Zhengrong; Li, Xi; Chen, Jing; Li, Min; Li, Huabin; He, Rui"

作者地址："[Chen, Yu; Wang, Zhe; Lai, Yangfan; Yin, Wei; Cai, Qian; Cai, Yiheng; Xue, Yushan; He, Rui] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Key Lab Med Mol Virol MOE NHC, Shanghai 200032, Peoples R China; [Chen, Yu; Wang, Zhe; Lai, Yangfan; Yin, Wei; Cai, Qian; Cai, Yiheng; Xue, Yushan; He, Rui] Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Shanghai 200032, Peoples R China; [Chen, Yu; Chen, Jing; He, Rui] Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai 200040, Peoples R China; [Song, Yan; Li, Min] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Clin Lab, Shanghai 200127, Peoples R China; [Han, Miaomiao; Li, Huabin] Fudan Univ, Affiliated Eye & ENT Hosp, Allergy Ctr, Dept Otolaryngol, Shanghai 200031, Peoples R China; [Chen, Zhengrong] Soochow Univ, Childrens Hosp, Dept Resp Dis, Suzhou, Peoples R China; [Li, Xi] Chongqing Med Univ, Biol Sci Inst, Chongqing 400032, Peoples R China; [Chen, Jing] Fudan Univ, Huashan Hosp, Dept Nephrol, Shanghai 200040, Peoples R China; [Li, Min] Shanghai Jiao Tong Univ, Fac Med Lab Sci, Sch Med, Shanghai 200127, Peoples R China; [He, Rui] Fudan Univ, Res Ctr Aging & Med, Shanghai 200040, Peoples R China"

通信作者："He, R (通讯作者)，Fudan Univ, Sch Basic Med Sci, Dept Immunol, Key Lab Med Mol Virol MOE NHC, Shanghai 200032, Peoples R China.; He, R (通讯作者)，Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Shanghai 200032, Peoples R China.; He, R (通讯作者)，Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai 200040, Peoples R China.; Li, HB (通讯作者)，Fudan Univ, Affiliated Eye & ENT Hosp, Allergy Ctr, Dept Otolaryngol, Shanghai 200031, Peoples R China.; He, R (通讯作者)，Fudan Univ, Res Ctr Aging & Med, Shanghai 200040, Peoples R China."

来源：CELLULAR & MOLECULAR IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001191084000002

JCR分区：Q1

影响因子：21.8

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Chemerin-CMKLR1; Staphylococcus aureus; Neutrophil; IL-33; Keratinocytes

摘要："The skin is the most common site of Staphylococcus aureus infection, which can lead to various diseases, including invasive and life-threatening infections, through evasion of host defense. However, little is known about the host factors that facilitate the innate immune evasion of S. aureus in the skin. Chemerin, which is abundantly expressed in the skin and can be activated by proteases derived from S. aureus, has both direct bacteria-killing activity and immunomodulatory effects via interactions with its receptor CMKLR1. Here, we demonstrate that a lack of the chemerin/CMKLR1 axis increases the neutrophil-mediated host defense against S. aureus in a mouse model of cutaneous infection, whereas chemerin overexpression, which mimics high levels of chemerin in obese individuals, exacerbates S. aureus cutaneous infection. Mechanistically, we identified keratinocytes that express CMKLR1 as the main target of chemerin to suppress S. aureus-induced IL-33 expression, leading to impaired skin neutrophilia and bacterial clearance. CMKLR1 signaling specifically inhibits IL-33 expression induced by cell wall components but not secreted proteins of S. aureus by inhibiting Akt activation in mouse keratinocytes. Thus, our study revealed that the immunomodulatory effect of the chemerin/CMKLR1 axis mediates innate immune evasion of S. aureus in vivo and likely increases susceptibility to S. aureus infection in obese individuals."

基金机构：Shanghai Science and Technology Commission; Key Laboratory of Medical Molecular Virology (MOE/NHC) [FDMVK-2021001]; National Natural Science Foundation of China [82271138]; National Key Research and Development Program of China [2020YFC2005003]; [23ZR1461500]

基金资助正文："This work was supported by Shanghai Science and Technology Commission 23ZR1461500 (to RH), Key Laboratory of Medical Molecular Virology (MOE/NHC) FDMVK-2021001 (to RH), The National Natural Science Foundation of China Grant 82271138 (to HL) and National Key Research and Development Program of China 2020YFC2005003 (to JC)."