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

作　　者：Yu Chen Yan Song Zhe Wang Yangfan Lai Wei Yin Qian Cai Miaomiao Han Yiheng Cai Yushan Xue Zhengrong Chen Xi Li Jing Chen Min Li Huabin Li Rui He 

机构地区：[1]Department of Immunology,Key Laboratory of Medical Molecular Virology(MOE/NHC),School of Basic Medical Sciences,and Shanghai Institute of Infectious Disease and Biosecurity,Fudan University,Shanghai,200032,China [2]National Clinical Research Center for Aging and Medicine,Huashan Hospital,Fudan University,Shanghai,200040,China [3]Department of Laboratory Medicine,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200127,China [4]Allergy Center,Department of Otolaryngology,Affiliated Eye and ENT Hospital,Fudan University,Shanghai,200031,China [5]Department of Respiratory Diseases,Children’s Hospital of Soochow University,Suzhou,China [6]Biology Science Institutes,Chongqing Medical University,Chongqing,400032,China [7]Department of Nephrology,Huashan Hospital,Fudan University,Shanghai,200040,China [8]Faculty of Medical Laboratory Science,Shanghai Jiaotong University School of Medicine,Shanghai,200127,China [9]Research Center of Allergy and Diseases,Fudan University,200040,Shanghai,China

出　　处：《Cellular & Molecular Immunology》2024年第6期533-545,共13页中国免疫学杂志（英文版）

基　　金：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);National Key Research and Development Program of China 2020YFC2005003(to JC).

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.

关 键 词：Chemerin-CMKLR1 Staphylococcus aureus NEUTROPHIL IL-33 KERATINOCYTES 

分 类 号：R392[医药卫生—免疫学] R75[医药卫生—基础医学]