Differences in immunoregulatory cytokine expression patterns in the systemic and genital tract compartments of HIV-1-infected commercial sex workers in Benin

Abstract

Initial exposure to human immunodeficiency virus type 1 (HIV-1) during heterosexual transmission occurs in the genital tract. Although much of the literature on the immune response to HIV-1 infection is based on studies performed at the systemic level, our understanding of tissue-specific immunity is lacking. Levels of both genital mucosal and blood interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma production were compared between 57 HIV-1-uninfected and 52 HIV-1-infected female commercial sex workers (CSWs) as well as 73 HIV-1-uninfected non-CSW control women at low risk for exposure. HIV-1-infected CSWs had significantly higher genital mucosal levels of TNF-alpha and IFN-gamma compared with those in both the HIV-uninfected CSW and non-CSW groups. In contrast, the serum levels of all the cytokines tested were lower in HIV-1-infected CSWs compared with those in the other groups. The increased production of genital mucosal pro-inflammatory cytokines in HIV-1-infected CSWs possibly reflects susceptibility to HIV-1 infection and disease progression/perpetuation at the initial site of exposure.

Figure 1

Distribution of IL-2, IL-6, IL-10, TNF-α, and IFN-γ CVL levels according to the study groups. CVL cytokine levels were quantified by BD Cytometric Bead Array and normalized to a standard curve. The LDL for each assay was 2.6 pg ml⁻ for IL-2, 3.0 pg ml⁻¹ for IL-6, 2.8 pg ml⁻¹ for IL-10 and TNF-α, and 7.1 pg ml⁻¹ for IFN-γ. Sample measurements below the LDL were assigned a value of 0. Values are expressed in pg ml⁻¹. Owing to the high number of samples below the assay LDL, cytokine levels were dichotomized as detectable and undetectable in all analyses. Comparisons of the cytokine detection rates (% of women producing cytokine levels above the LDL) between two study groups were examined with the χ² test. Significant (or near significant) differences in the cytokine detection rates between the two groups are shown. Differences that were not statistically significant are not illustrated. CVL, cervicovaginal lavage; IFN, interferon; IL, interleukin; LDL, lower detection limit; TNF, tumor necrosis factor.

Figure 2

Distribution of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ serum levels according to the study groups. Serum cytokine levels were quantified by BD Cytometric Bead Array and normalized to a standard curve. The LDL for each assay was 2.6 pg ml⁻¹ for IL-2 and IL-4, 3.0 pg ml⁻¹ for IL-6, 2.8 pg ml⁻¹ for IL-10 and TNF-α, and 7.1 pg ml⁻¹ for IFN-γ. Sample measurements below the LDL were assigned a value of 0. Values are expressed in pg ml⁻¹. Owing to the high number of samples below the assay LDL, cytokine levels were dichotomized as detectable and undetectable in all analyses. Comparisons of the cytokine detection rates (% of women producing cytokine levels above the LDL) between two study groups were examined with the χ² test. Significant (or near significant) differences in the cytokine detection rates between the two groups are shown. Differences that were not statistically significant are not illustrated. IFN, interferon; IL, interleukin; LDL, lower detection limit; TNF, tumor necrosis factor.