Mycoplasma genitalium infection activates cellular host defense and inflammation pathways in a 3-dimensional human endocervical epithelial cell model.

BACKGROUND Because Mycoplasma genitalium is a prevalent and emerging cause of sexually transmitted infections, understanding the mechanisms by which M. genitalium elicits mucosal inflammation is an essential component to managing lower and upper reproductive tract disease syndromes in women. METHODS We used a rotating wall vessel bioreactor system to create 3-dimensional (3-D) epithelial cell aggregates to model and assess endocervical infection by M. genitalium. RESULTS Attachment of M. genitalium to the host cell's apical surface was observed directly and confirmed using immunoelectron microscopy. Bacterial replication was observed from 0 to 72 hours after inoculation, during which time host cells underwent ultrastructural changes, including reduction of microvilli, and marked increases in secretory vesicle formation. Using genome-wide transcriptional profiling, we identified a host defense and inflammation signature activated by M. genitalium during acute infection (48 hours after inoculation) that included cytokine and chemokine activity and secretion of factors for antimicrobial defense. Multiplex bead-based protein assays confirmed secretion of proinflammatory cytokines, several of which are involved in leukocyte recruitment and hypothesized to enhance susceptibility to human immunodeficiency type 1 infection. CONCLUSIONS These findings provide insight into key molecules and pathways involved in innate recognition of M. genitalium and the response to acute infection in the human endocervix.