commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures共生的细菌调节阴道上皮细胞多层文化的先天免疫反应.pdf

Commensal Bacteria Modulate Innate Immune Responses of Vaginal Epithelial Cell Multilayer Cultures 1¤a 2¤b 3 1 William A. Rose II , Chris L. McGowin , Rae Ann Spagnuolo , Tonyia D. Eaves-Pyles , Vsevolod L. Popov2, Richard B. Pyles1,3* 1 Department of Microbiology and Immunology, University of Texas Medical Branch, Glaveston, Texas, United States of America, 2 Department of Pathology, University of Texas Medical Branch, Glaveston, Texas, United States of America, 3 Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States of America Abstract The human vaginal microbiome plays a critical but poorly defined role in reproductive health. Vaginal microbiome alterations are associated with increased susceptibility to sexually-transmitted infections (STI) possibly due to related changes in innate defense responses from epithelial cells. Study of the impact of commensal bacteria on the vaginal mucosal surface has been hindered by current vaginal epithelial cell (VEC) culture systems that lack an appropriate interface between the apical surface of stratified squamous epithelium and the air-filled vaginal lumen. Therefore we developed a reproducible multilayer VEC culture system with an apical (luminal) air-interface that supported colonization with selected commensal bacteria. Multilayer VEC developed tight-junctions and other hallmarks of the vaginal mucosa including predictable proinflammatory cytokine secretion following TLR stimulation. Colonization of multilayers by common vaginal commensals including Lactobacillus crispatus, L. jensenii, and L. rhamn