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天花疫苗接种会引起共生皮肤细菌的大量增加,这些细菌会促进发病机制并影响宿主反应。

Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and influence the host response.

机构信息

Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Maurice Müller Laboratories, Department for Biomedical Research, Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, University of Bern, Bern, Switzerland.

出版信息

PLoS Pathog. 2022 Apr 21;18(4):e1009854. doi: 10.1371/journal.ppat.1009854. eCollection 2022 Apr.

Abstract

Interactions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and influence the host response. Treatment of vaccinated specific-pathogen-free (SPF) mice with antibiotic, or infection of genetically-matched germ-free (GF) animals caused smaller lesions without alteration in virus titre. Tissue damage correlated with enhanced neutrophil and T cell infiltration and levels of pro-inflammatory tissue cytokines and chemokines. One month after vaccination, GF and both groups of SPF mice had equal numbers of VACV-specific CD8+ T cells and were protected from disease induced by VACV challenge, despite lower levels of VACV-neutralising antibodies observed in GF animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV and influence the host response to vaccination.

摘要

病原体、宿主微生物群和免疫系统之间的相互作用影响着许多生理和病理过程。在 20 世纪,广泛的皮肤接种牛痘病毒(VACV)导致了天花的根除,但 VACV 如何与微生物群相互作用,以及这是否会影响疫苗接种的效果,在很大程度上仍是未知的。在这里,我们报告称,VACV 的皮内接种会导致感染组织中共生细菌数量的大量增加,从而增强炎症细胞的募集,促进组织损伤,并影响宿主反应。用抗生素治疗接种的无特定病原体(SPF)小鼠,或感染遗传匹配的无菌(GF)动物,会导致病变更小,而不会改变病毒滴度。组织损伤与中性粒细胞和 T 细胞浸润的增强以及促炎组织细胞因子和趋化因子的水平相关。接种一个月后,GF 和两组 SPF 小鼠都有等量的 VACV 特异性 CD8+T 细胞,并且能够免受 VACV 攻击引起的疾病的影响,尽管在 GF 动物中观察到的 VACV 中和抗体水平较低。因此,皮肤微生物群可能在 VACV 接种期间提供一种类佐剂刺激,并影响宿主对疫苗接种的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42e5/9022886/7d5311316e06/ppat.1009854.g001.jpg

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