The Cervicovaginal Microbiota-Host Interaction Modulates Chlamydia trachomatis Infection

mBio

Jeanne Tamarelle¹  Larry J. Forney²  Patrik M. Bavoil³  Samuel K. Lai⁴  Alison M. Schaefer⁴  Katrina S. Mark⁵  Mishka Terplan⁵  Kathleen Gwilliam⁶  Rebecca M. Brotman⁶  Michael S. Humphrys⁶  Jacques Ravel⁶  Steven B. Smith⁶  Elias J. McComb⁶  Pawel Gajer⁶  Vonetta L. Edwards⁶  Bing Ma⁶ 

[1] Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases, Institut Pasteur, INSERM, Université de Versailles-Saint-Quentin-en-Yvelines, Versailles, France;Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA;Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA;Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland, USA;Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA;

关键词: Lactobacillus;    epigenetic;    lactic acid;    microbiome;    proliferation;    sexually transmitted infection;   

DOI  :  10.1128/mBio.01548-19

来源: DOAJ

【 摘 要 】

ABSTRACT The mechanism(s) by which Lactobacillus-dominated cervicovaginal microbiota provide a barrier to Chlamydia trachomatis infection remain(s) unknown. Here we evaluate the impact of different Lactobacillus spp. identified via culture-independent metataxonomic analysis of C. trachomatis-infected women on C. trachomatis infection in a three-dimensional (3D) cervical epithelium model. Lactobacillus spp. that specifically produce d(−) lactic acid were associated with long-term protection against C. trachomatis infection, consistent with reduced protection associated with Lactobacillus iners, which does not produce this isoform, and with decreased epithelial cell proliferation, consistent with the observed prolonged protective effect. Transcriptomic analysis revealed that epigenetic modifications involving histone deacetylase-controlled pathways are integral to the cross talk between host and microbiota. These results highlight a fundamental mechanism whereby the cervicovaginal microbiota modulates host functions to protect against C. trachomatis infection. IMPORTANCE The vaginal microbiota is believed to protect women against Chlamydia trachomatis, the etiologic agent of the most prevalent sexually transmitted infection (STI) in developed countries. The mechanism underlying this protection has remained elusive. Here, we reveal the comprehensive strategy by which the cervicovaginal microbiota modulates host functions to protect against chlamydial infection, thereby providing a novel conceptual mechanistic understanding. Major implications of this work are that (i) the impact of the vaginal microbiota on the epithelium should be considered in future studies of chlamydial infection and other STIs and (ii) a fundamental understanding of the cervicovaginal microbiota’s role in protection against STIs may enable the development of novel microbiome-based therapeutic strategies to protect women from infection and improve vaginal and cervical health.

【 授权许可】

Unknown