Histological Evidence of Chronic Mycoplasma genitalium-Induced Cervicitis in HIV-Infected Women: A Retrospective Cohort Study

Abstract

Background: Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in inflammatory syndromes of the female reproductive tract. The objective of this study was to investigate human immunodeficiency virus (HIV)-infected women for an association between M. genitalium and cervicitis, a putative mechanism for enhanced HIV transmission efficiency to an uninfected partner.

Methods: Using a longitudinal cohort of antiretroviral therapy-adherent New Orleans women, we retrospectively screened for M. genitalium and quantitatively characterized several markers of cervical inflammation, including secreted cytokines and cytological and histological signs of leukocyte infiltration.

Results: We observed a high prevalence of M. genitalium (7.4%) among HIV-infected New Orleans women. Chronic M. genitalium infection was associated with increased secretion of proinflammatory cytokines, including interleukin 1β, interleukin 6, and interleukin 8, and marked inflammatory cervical infiltrates in the cervix with enrichment of HIV target cells. Cure of M. genitalium infection resulted in ablation of all signs of inflammation.

Conclusions: These findings implicate M. genitalium as an etiologic agent of cervicitis in HIV-infected women, providing a potential mechanism for enhanced HIV transmission to an uninfected partner. Screening and treatment of M. genitalium among HIV-infected individuals may be warranted to further understand this coinfection scenario, improve cervical health, and reduce the spread of HIV.

Keywords: AIDS; HIV; Mycoplasma genitalium; cervical inflammation; cervicitis; inflammation; sexually transmitted infection.

Figure 1.

Secreted cervical cytokine response during chronic Mycoplasma genitalium infection. A comprehensive panel of cytokines was quantitatively analyzed in cervicovaginal lavage specimens from women chronically infected with M. genitalium, using multiplex cytometric bead arrays. The complete results are shown in the Supplementary Data. *P < .05, by the Student t test. Abbreviations: IL-1β, interleukin 1β; IL-6, interleukin 6; IL-8; interleukin 8; MDC, macrophage-derived chemokine.

Figure 2.

Cervical leukocyte quantification during chronic Mycoplasma genitalium infection and after cure. The ratio of leukocytes to epithelial cells was calculated using ThinPrep PreservCyt specimens collected from women with chronic M. genitalium infection and a randomly selected subset of 22 negative specimens. A, Composite analysis of specimens from all M. genitalium–positive subjects and those who never tested positive. B–D, Individual longitudinal analyses of 3 study subjects who were chronically infected with M. genitalium and individuals who never tested positive. Data are expressed as the mean ratio of leukocytes to epithelial cells per high-powered microscope field. *P < .05, by the Student t test.

Figure 3.

Characterization of cervical leukocytic infiltrates by immunohistochemical analysis. Representative paraffin-embedded cervical curettage specimens from subject 3 were probed using markers of neutrophils (A; elastase), monocytes/macrophages (B; CD68), and T cells (C; CD3) while chronically infected with Mycoplasma genitalium (middle column) and after cure (right column). The positive controls for each antibody (left column) are demonstrated by positive staining in human tonsil sections for CD68 (B) and CD3 (C); specificity of the neutrophil elastase antibody is verified by positive staining of distinct polymorphonuclear cell infiltrates in endocervical curettage specimens (A, inset). Arrows denote cells staining positive for the indicated cellular marker. Tonsil fields in panels B and C are 100× original magnification; all other fields 400× original magnification.

Figure 4.

Quantitative comparison of leukocytic infiltrates during chronic Mycoplasma genitalium infection and after cure. Immunohistochemical findings for neutrophils (elastase), monocytes/macrophages (CD68), and T cells (CD3⁺, CD4⁺, and CD8⁺) in endocervical curettage specimens were quantitatively analyzed for 2 chronically infected subjects (subjects 1 and 3). The 3,3′-diaminobenzidine (DAB) signal was compared between curettage specimens obtained while chronically infected with M. genitalium and following cure. Results are expressed as the DAB signal per total nuclear area (TNA) in 5 high-powered microscope fields. P < .05, by the Student t test, compared with after cure.