Modulation of Pulmonary Microbiota by Antibiotic or Probiotic Aerosol Therapy: A Strategy to Promote Immunosurveillance against Lung Metastases

免疫监视 医学 抗生素治疗 抗生素 益生菌 免疫学 免疫系统 肺脓肿 肠道菌群 生物 微生物学 内科学 细菌 遗传学
作者
Valentino Le Noci,Simone Guglielmetti,Stefania Arioli,Chiara Camisaschi,Francesca Bianchi,Michele Sommariva,Chiara Storti,Tiziana Triulzi,Chiara Castelli,Andrea Balsari,Elda Tagliabue,Lucia Sfondrini
出处
期刊:Cell Reports [Cell Press]
卷期号:24 (13): 3528-3538 被引量:180
标识
DOI:10.1016/j.celrep.2018.08.090
摘要

Highlights•Aerosolized antibiotic reduces lung microbiota and a tolerogenic microenvironment•Aerosol delivery of an antibiotic or probiotic decreases tumor seeding in the lung•Antibiotic or probiotic aerosol improves chemotherapy against experimental metastasesSummaryPulmonary immunological tolerance to inhaled particulates might create a permissive milieu for lung metastasis. Lung microbiota contribute to pulmonary tolerance; here, we explored whether its manipulation via antibiotic or probiotic aerosolization favors immune response against melanoma metastasis. In lungs of vancomycin/neomycin-aerosolized mice, a decrease in bacterial load was associated with reduced regulatory T cells and enhanced T cell and NK cell activation that paralleled a significant reduction of melanoma B16 lung metastases. Reduction of metastases also occurred in lungs transplanted with bacterial isolates from antibiotic-treated lungs. Aerosolized Lactobacillus rhamnosus strongly promoted immunity against B16 lung metastases as well. Furthermore, probiotics or antibiotics improved chemotherapy activity against advanced B16 metastases. Thus, we identify a role for lung microbiota in metastasis and show that its targeting via aerosolization is a therapy that can prevent metastases and enhance responses to chemotherapy.Graphical abstract
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