Virginia J. Glick, Cecilia A. Webber, Lauren E. Simmons, Morgan C. Martin, Maryam Ahmad, Cecilia H. Kim, Amanda N.D. Adams, Sunghee Bang, Michael C. Chao, Nicole C. Howard, Sarah M. Fortune, Manasvi Verma, Marco Jost, Lalit K. Beura, Michael J. James, Seo Yoon Lee, Caroline M. Mitchell, Jon Clardy, Ki Hyun Kim, Smita Gopinath
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引用次数: 0
Abstract
The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that Lactobacillus crispatus, a key vaginal bacterial species, produces a family of β-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory β-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation.
期刊介绍:
Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.