Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
J Autoimmun. 2018 Sep;93:104-113. doi: 10.1016/j.jaut.2018.07.003. Epub 2018 Jul 7.
Perturbation of commensal bacteria by antibiotic exposure aggravates ovalbumin (OVA)-induced allergic asthma in pre-weaning mice. However, the influence of dysbiosis of commensal bacteria on asthma development in post-weaning mice is still limited. Here, we treated 3-week-old post-weaning mice with antibiotics to disrupt commensal bacteria and then established OVA-induced allergic asthma by peritoneal sensitization using OVA/alum and intranasal challenge with OVA. Contrary to the protective function in pre-weaning mice, commensal bacteria in post-weaning mice aggravated OVA-induced asthma. Commensal bacteria in post-weaning mice promoted OVA-induced allergic asthma through maintenance of NLRP3/IL-1β expression in peritoneal macrophages (pMφ), which promoted recruitment of inflammatory cells, especially inflammatory monocytes, into the peritoneal cavity after OVA/alum sensitization. Further study showed that metronidazole- and vancomycin-sensitive bacteria are involved in maintenance of NLRP3/IL-1β signal in pMφ. Our results suggest that certain species of commensal bacteria in post-weaning mice aggravate OVA-induced allergic asthma through NLRP3/IL-1β signal pathway.
抗生素暴露引起的共生菌失调会加重幼鼠期卵清蛋白（OVA）诱导的过敏性哮喘。然而，共生菌失调对幼鼠期后哮喘发展的影响仍有限。在这里，我们用抗生素处理 3 周龄的幼鼠以破坏共生菌，然后通过 OVA/明矾腹腔致敏和 OVA 鼻腔内挑战建立 OVA 诱导的过敏性哮喘。与幼鼠中的保护功能相反，幼鼠期后的共生菌加剧了 OVA 诱导的哮喘。共生菌通过维持腹腔巨噬细胞（pMφ）中的 NLRP3/IL-1β 表达，促进 OVA/明矾致敏后炎症细胞，特别是炎症单核细胞向腹腔内的募集，从而促进 OVA 诱导的过敏性哮喘。进一步的研究表明，甲硝唑和万古霉素敏感细菌参与了 pMφ 中 NLRP3/IL-1β 信号的维持。我们的结果表明，幼鼠期后的某些共生菌通过 NLRP3/IL-1β 信号通路加重 OVA 诱导的过敏性哮喘。
