Characterization of the Genital Mucosa Immune Profile to Distinguish Phases of the Menstrual Cycle: Implications for HIV Susceptibility

• Published in: The Journal of infectious diseases 2019-02, Vol.219 (6), p.856-866
• Main Authors: Boily-Larouche, Geneviève, Lajoie, Julie, Dufault, Brenden, Omollo, Kenneth, Cheruiyot, Juliana, Njoki, Jane, Kowatsch, Monika, Kimani, Makobu, Kimani, Joshua, Oyugi, Julius, Fowke, Keith R
• Format: Article
• Language: English
• Subjects: Biomarkers - analysis; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD69 antigen; Cell activation; Cervix Uteri - cytology; Cervix Uteri - immunology; Chemokine CCL2 - analysis; Cytokines; Disease transmission; Female; HIV; HIV Infections - immunology; HIV Infections - transmission; Human immunodeficiency virus; Humans; Immunological memory; Immunomodulation; Kenya; Leukocytes (mononuclear); Lymphocytes T; Major and Brief Reports; Memory cells; Menstrual cycle; Menstrual Cycle - immunology; Menstruation; Monocyte chemoattractant protein 1; Mucosal immunity; Sex industry; Sex Workers; Vagina; Vagina - cytology; Vagina - immunology; Vaginosis; Vaginosis, Bacterial - immunology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiy585

Here, we compared the impact of endogenous sexual hormones on the mucosal immune response. Our study shows that the follicular phase of the menstrual cycle was associated with elevated level of cervical CCL2 and retention of resident memory CD4+ T cells. Abstract Background Inflammation and immune activation are key factors in sexual transmission of human immunodeficiency virus (HIV). We sought to define the impact of hormonal cycling on the mucosal immune environment and HIV risk in sex workers with a natural menstrual cycle. Methods We compared soluble mucosal immune factors and cervical mononuclear cells during hormone titer–defined phases of the menstrual cycle among 37 sex workers from Nairobi, Kenya. Systemic and mucosal samples were collected 14 days apart to distinguish the follicular and luteal phases of the menstrual cycle, and phases were confirmed by hormone measurements. Vaginal concentrations of 19 immune modulators and cervical T-cell activation markers were measured. Results The follicular phase signature was characterized by an elevated CCL2 level, decreased interleukin 1α and interleukin 1β cervical concentrations, and a significant increase in the proportion of CD4+ T cells that expressed CD69. The genital concentration of CCL2 was the best marker to distinguish the follicular from the luteal phase in univariate and multivariate analyses and remained independent of elevated genital inflammation and bacterial vaginosis. Conclusion The follicular phase of the menstrual cycle was associated with an elevated CCL2 level and retention of resident memory CD4+ T cells, which has implications for increased susceptibility to HIV infection.