Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1ß and Lactoferrin

Abstract

BackgroundMore than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects.Methodology/Principal Findings32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis.Conclusions/SignificanceThese studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site.

DoAtopobium vaginae, Megasphaerasp. andLeptotrichiasp. change the local innate immune response and sialidase activity in bacterial vaginosis?

“…When analysing the current data on cytokines in BV samples, a positive correlation can be observed on the levels of IL-1β, IL-6 and IL-8. These findings are partially supported by Spear et al 34 who showed a positive correlation on vaginal levels of IL-1β, IL-6 and TNF-α, but failed to demonstrate a correlation between IL-6 and IL-8, although their study did not evaluate women with BV exclusively.…”

Associations Between Genital Tract Infections, Genital Tract Inflammation, and Cervical Cytobrush HIV-1 DNA in US Versus Kenyan Women

“…Across studies, BV is associated with IL-1β in both US 17, 18 and Kenyan 19 women, but few reports examined IL-1β and other infections. IL-6 appears to have little relationship with any genital infection 17, 20-22 , while increased IL-8 has been associated with trichomoniasis, 23 cervicitis, 24 and yeast 25 in many, but not all 17, 25 studies. Few of these studies enrolled African women, thus we are unable to assess whether the differences we observed in associations between US and Kenyan women are an anomaly, or reflect regional differences.…”

The Role of Bacterial Vaginosis and Trichomonas in HIV Transmission Across The Female Genital Tract

“…To detect lactoferrin, custom cytometric bead arrays were made by coupling blank beads with rabbit antibody to lactoferrin. All bead arrays were assayed on a FacsCalibur and levels of cytokines calculated using BD CBA software (BD Biosciences [106]).…”