PNAS:抗生素治疗可影响抗病毒免疫力

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近日，对小鼠的一项研究提示，抗生素治疗可能与对某些病毒感染的免疫力被削弱有关联。

人类阴道有大量的乳酸杆菌物种，它们维持了一个酸性环境并且产生了过氧化氢用于抵御致病菌。Heung Kyu Lee及其同事测试了被抗生素治疗触发的阴道微生物区系的不平衡是否会削弱针对生殖器疱疹的免疫力，这种感染是由单纯疱疹病毒2型（HSV-2）引起的。与获得了蒸馏水的小鼠相比，用5种口服抗生素的组合治疗了4周的小鼠应对阴道内单纯疱疹病毒2型（HSV-2）感染的成功较少，表现出了更严重的病理，更高的阴道病毒滴定度，以及轻度增加的死亡率。


尽管抗生素没有影响根据促炎性细胞因子的水平衡量的固有免疫应答，抗生素治疗改变了阴道细菌群落的组成，特别是诱导产生了不利于乳酸杆菌的革兰氏阴性蛋白菌的增加。抗生素治疗还与阴道分泌IL-33的增加联系在了一起，这是一种细胞因子，能削弱效应T细胞迁移到阴道黏膜的感染部位，并且通过减少细胞因子IFN-γ这种人类主要的抗病毒防御力量，遏制了局部抗病毒免疫力；对重组IL-33的实验支持了这些发现。IL-33水平的增加很可能是由制造蛋白酶的细菌诱导产生的，这些细菌在口服抗生素存在的情况下丰富地生长。


实验结果表明，抗生素诱导的黏膜表面微生物平衡的破坏可能影响人类抗病毒免疫防御。


来源：生物360

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Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Ji Eun Oha, Byoung-Chan Kimb, Dong-Ho Changb, Meehyang Kwonc, Sun Young Leec, Dukjin Kangc, Jin Young Kimd, Inhwa Hwange, Je-Wook Yue, Susumu Nakaef,g, and Heung Kyu Leea,1

Commensal microbiota are well known to play an important role in antiviral immunity by providing immune inductive signals; however, the consequence of dysbiosis on antiviral immunity remains unclear. We demonstrate that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. However, innate immune responses, including type I IFN and proinflammatory cytokine production at infection sites, as well as induction of virus-specific CD4 and CD8 T-cell responses in draining lymph nodes, were not impaired in antibiotic-treated mice. By screening the factors controlling antiviral immunity, we found that IL-33, an alarmin released in response to tissue damage, was secreted from vaginal epithelium after the depletion of commensal microbiota. This cytokine suppresses local antiviral immunity by blocking the migration of effector T cells to the vaginal tissue, thereby inhibiting the production of IFN-γ, a critical cytokine for antiviral defense, at local infection sites. These findings provide insight into the mechanisms of homeostasis maintained by commensal bacteria, and reveal a deleterious consequence of dysbiosis in antiviral immune defense.

http://www.pnas.org/content/earl ... 2-8534-1f7c30ef1789