The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens  

作　　者：Alexandra Stream Ross Corriden Simon Döhrmann Richard L.Gallo Victor Nizet Ericka L.Anderson 

机构地区：[1]Division of Host-Microbe Systems and Therapeutics,Department of Pediatrics,University of California San Diego School of Medicine,La Jolla,California,USA [2]Department of Dermatology,University of California San Diego School of Medicine,La Jolla,California,USA [3]Skaggs School of Pharmacy and Pharmaceutical Sciences,University of California San Diego,La Jolla,California,USA

出　　处：《Infectious Microbes & Diseases》2024年第2期65-73,共9页感染微生物与疾病（英文）

基　　金：US National Institutes of Health grants(R01-AI145325 to VN and R37-AI052453 to VN and RLG);a BioLegend Graduate Fellowship in Immunology.

摘　　要：Vitamin A and its biologically active derivative,retinoic acid(RA),are important for many immune processes.RA,in particular,is essential for the development of immune cells,including neutrophils,which serve as a front-line defense against infection.Although vitamin A deficiency has been linked to higher susceptibility to infections,the precise role of vitamin A/RA in host-pathogen interactions remains poorly understood.Here,we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus(MRSA).RA treatment stimulated primary human neutrophils to produce reactive oxygen species,neutrophil extracellular traps and the antimicrobial peptide cathelicidin(LL-37).Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection,we expanded our analysis to other infectious agents.RA did not affect the growth of a number of common bacterial pathogens,including MRSA,Escherichia coli K1 and Pseudomonas aeruginosa;however,RA directly inhibited the growth of group A Streptococcus(GAS).This antimicrobial effect,likely in combination with RA-mediated neutrophil boosting,resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of RA.Furthermore,in a murine model of GAS skin infection,topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial burden.These findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

关 键 词：retinoic acid NEUTROPHIL bacterial infection Staphylococcus aureus group A Streptococcus neutrophil extracellular traps antimicrobial peptide CATHELICIDIN 

分 类 号：R756[医药卫生—皮肤病学与性病学]