Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression

• Published in: PloS one 2015-11, Vol.10 (11), p.e0141717-e0141717
• Main Authors: Huang, Fei, Qiao, Hong-Mei, Yin, Jia-Ning, Gao, Yang, Ju, Yang-Hua, Li, Ya-Nan
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Allergies; Animals; Animals, Newborn; Asthma; Asthma - immunology; Asthma - microbiology; Babies; Bacteria; Campeloma leptum; Care and treatment; Cesarean section; Clostridium; Clostridium - immunology; Clostridium Infections - complications; Clostridium Infections - immunology; Comparative analysis; Cytokines; Development and progression; Disease; Disease Models, Animal; Exposure; Female; Growth factors; Health aspects; Helper cells; Hospitals; Immune Tolerance; Immunity; Immunity, Cellular; Immunosuppression; Immunotherapy; Infants; Infiltration; Inflammation; Lung - immunology; Lung - microbiology; Lungs; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Microbiota; Molecular biology; Newborn babies; Ovalbumin; Ovalbumin - immunology; Pathogenesis; Patient outcomes; Pediatrics; Respiratory tract; Risk factors; Rodents; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - microbiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141717

Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice. We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA). Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses. These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.