한빛사논문
Young Jae Kima,b,c,d*, June-Young Leee,f*, Jae Jin Leeg*, Sang Min Jeona,b,c,d*, Prashanta Silwala,b, In Soo Kima,b,c, Hyeon Ji Kima,b,c, Cho Rong Parka,b,c, Chaeuk Chungb,h, Jeong Eun Hane, Jee-Won Choie, Euon Jung Take,f, JiHo Yoof, Su-Won Jeonge, Do-Yeon Kime, Warisa Ketphang, Su-Young Kimi, Byung Woo Jhuni, Jake Whangj, JinMan Kimk, Hyungjin Eohg#, Jin-Woo Baee,f#, and Eun-Kyeong Joa,b,c#
aDepartment of Microbiology, Chungnam National University School of Medicine Daejeon, Korea; bInfection Control Convergence Research Center, Chungnam National University School of Medicine Daejeon, Korea; cDepartment of Medical Science, Chungnam National University School of Medicine Daejeon, Korea; dBrain Korea 21 FOUR Project for Medical Science, Chungnam National University School of Medicine Daejeon, Korea; eDepartment of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, Korea; fDepartment of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea; gDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California CA, USA; hDivision of Pulmonary and Critical Care, Department of Internal Medicine, Chungnam National University School of Medicine Daejeon, Korea; iDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul, South Korea; jKorea Mycobacterium Resource Center (KMRC) & Basic Research Section, The Korean Institute of Tuberculosis (KIT), Cheongju, Korea; kDepartment of Pathology, Chungnam National University School of Medicine, Daejeon, Korea
*These authors contributed equally to this work.
#Corresponding author.
Abstract
Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut–lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut–lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with Bifidobacterium species. Notably, oral treatment with either Bifidobacterium pseudolongum or inosine enhanced antimicrobial pulmonary immune defense against NTM infection, even with multidrug-resistant clinical NTM strains. Our findings indicate that l-arginine-induced gut microbiota remodeling with enrichment of B. pseudolongum boosts pulmonary immune defense against NTM infection by driving the protective gut–lung axis in vivo.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
관련분야 논문보기