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

Chris L. McGowin, Andrea L. Radtke, Kyle Abraham, David H. Martin, Melissa Herbst-Kralovetz

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1857-1868
Number of pages12
JournalJournal of Infectious Diseases
Volume207
Issue number12
DOIs
StatePublished - Jun 15 2013

Fingerprint

Mycoplasma genitalium
Mycoplasma Infections
Epithelial Cells
Inflammation
Infection
Cytokines
Immunoelectron Microscopy
Secretory Vesicles
Bioreactors
Sexually Transmitted Diseases
Microvilli
Chemokines
Leukocytes
Genome

Keywords

  • cervix
  • endocervix
  • epithelial
  • immune response
  • Mycoplasma
  • Mycoplasma genitalium
  • sexually transmitted infection
  • transcriptome

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Mycoplasma genitalium infection activates cellular host defense and inflammation pathways in a 3-dimensional human endocervical epithelial cell model. / McGowin, Chris L.; Radtke, Andrea L.; Abraham, Kyle; Martin, David H.; Herbst-Kralovetz, Melissa.

In: Journal of Infectious Diseases, Vol. 207, No. 12, 15.06.2013, p. 1857-1868.

Research output: Contribution to journalArticle

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