The Cervicovaginal Microbiota-Host Interaction Modulates <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Infection
Vonetta L. Edwards,
Steven B. Smith,
Elias J. McComb,
Jeanne Tamarelle,
Bing Ma,
Michael S. Humphrys,
Pawel Gajer,
Kathleen Gwilliam,
Alison M. Schaefer,
Samuel K. Lai,
Mishka Terplan,
Katrina S. Mark,
Rebecca M. Brotman,
Larry J. Forney,
Patrik M. Bavoil,
Jacques Ravel
Affiliations
Vonetta L. Edwards
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Steven B. Smith
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Elias J. McComb
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Jeanne Tamarelle
Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases, Institut Pasteur, INSERM, Université de Versailles-Saint-Quentin-en-Yvelines, Versailles, France
Bing Ma
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Michael S. Humphrys
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Pawel Gajer
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Kathleen Gwilliam
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Alison M. Schaefer
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Samuel K. Lai
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Mishka Terplan
Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland, USA
Katrina S. Mark
Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland, USA
Rebecca M. Brotman
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Larry J. Forney
Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA
Patrik M. Bavoil
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA
Jacques Ravel
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
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.
