Relationship between Levels of Inflammatory Cytokines in the Genital Tract and CD4⁺Cell Counts in Women with Acute HIV‐1 Infection

Abstract

Inflammatory responses at mucosal surfaces after human immunodeficiency virus type 1 (HIV-1) transmission may influence disease outcome. We evaluated levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, IL-8, IL-10, and IL-12 in genital tract and plasma specimens from 44 women with acute HIV infection and 29 HIV-negative control women (13 of whom were women in the acute HIV infection cohort who had preinfection samples available for analysis). Women with acute HIV infection had significantly elevated levels of IL-6, IL-10, and IL-12 in genital tract specimens and elevated levels of IL-1beta, IL-8, and IL-10 in plasma specimens, compared with HIV-negative control women. Levels of IL-1beta, IL-6, and IL-8 in cervicovaginal specimens from women with acute HIV infection showed a significant inverse correlation with systemic CD4(+) cell counts, suggesting that mucosal inflammation is associated with low CD4(+) cell counts during acute HIV infection.

Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention

“…These data agree with previous studies, showing increased soluble proinflammatory markers in the genital tracts of HIV-infected individuals (34,35). It is important to note that the women in our study were on a successful cART regime, which means that treatment suppressed viral load but did not fully suppress inflammation in the FGT.…”

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

“…The GR ligands used in this study were dexamethasone (Calbiochem), cortisol (Sigma), hydrocortisone (Sigma), prednisolone (Calbiochem), RU-486 (Calbiochem), and norethisterone acetate (NEA) (Sigma). The PPAR␥ ligands ciglitazone, rosiglitazone, pioglitazone, troglitazone, 15-deoxy⌬ 12,14 -prostagladin J 2 , MC-555, and GW9662 were purchased from Cayman Chemicals. Ligands were reconstituted in either dimethyl sulfoxide (DMSO) or ethanol by following the manufacturer's instructions.…”

“…It is important to note that these ligand-activated NRs repress HIV-1 expression in response to stimulation with concentrations of TNF-␣, IL-6, and IL-8 expected at local sites where HIV-1-infected macrophages reside in vivo (Fig. 10) (14,101). It is unlikely that the effects on HIV-1 replication in U1 and J1.1 cells are due to carryover of NR ligands for three reasons.…”

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

“…18). Increased levels of genital tract proinflammatory cytokines can promote viral replication in the mucosa and thereby recruit immune target cells leading to increased HIV shedding (19)(20)(21). When an HIV-infected sexual partner is involved, HIV particles in the seminal fluid and the fluid itself may also cause genital epithelial damage and further inflammation (22,23).…”

“…This immune activation can result in influx of HIV target cells and upregulation of CD4, CCR5, and CLR expression on selected cell populations in the genital tissue. Genital inflammation may increase HIV acquisition and heighten the plasma viral load's set point (19,20). In this study, in a unique collection of genital tissue samples from HIV-infected women, we assessed the distribution of the HIVbinding receptors CD4, CCR5, Langerin, DC-SIGN, and MR. By using a panel of proinflammatory molecules, we further defined the immune activation status in the ectocervical mucosa for a comparison between HIV-infected and -uninfected women.…”