TY - JOUR
T1 - Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner
AU - Doerflinger, Sylvie Y.
AU - Throop, Andrea L.
AU - Herbst-Kralovetz, Melissa M.
N1 - Funding Information:
Financial support. This work was supported, in part, by the Alternatives Research and Development Foundation (grant to M. M. H-K.). Potential conflicts of interest. All authors: No reported conflicts.
PY - 2014/6/15
Y1 - 2014/6/15
N2 - Background. Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health. Methods. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia). Results. Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8. Conclusions. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.
AB - Background. Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health. Methods. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia). Results. Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8. Conclusions. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.
KW - Atopobium vaginae
KW - Lactobacillus spp.
KW - Prevotella bivia
KW - antimicrobial peptides
KW - barrier function
KW - epithelial cell
KW - female reproductive tract
KW - innate immunity
KW - mucin
KW - sexually transmitted infection
KW - toll-like receptor
KW - vagina
KW - vaginal microbiota and bacterial vaginosis
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U2 - 10.1093/infdis/jiu004
DO - 10.1093/infdis/jiu004
M3 - Article
C2 - 24403560
AN - SCOPUS:84900525927
SN - 0022-1899
VL - 209
SP - 1989
EP - 1999
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -