한빛사논문
Virginia J. Glick,1,7 Cecilia A. Webber,1,7 Lauren E. Simmons,1 Morgan C. Martin,1 Maryam Ahmad,1 Cecilia H. Kim,1 Amanda N.D. Adams,1 Sunghee Bang,2 Michael C. Chao,1 Nicole C. Howard,1 Sarah M. Fortune,1 Manasvi Verma,3 Marco Jost,3 Lalit K. Beura,4 Michael J. James,2 Seo Yoon Lee,5 Caroline M. Mitchell,6 Jon Clardy,2 Ki Hyun Kim,2,5,* and Smita Gopinath1,8,*
1Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Blavatnik Institute, Boston, MA 02115, USA
3Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
4Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
5School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
6Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
7These authors contributed equally
8Lead contact
*Correspondence: K.H.K., S.G.
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.
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