A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers

Lajoie, Julie; Juno, Jennifer A; Burgener, Adam; Rahman, Syeda; Mogk, Kenzie; Wachihi, Charles; Mwanjewe, J; Plummer, Frank; Kimani, Joshua; Ball, T. Blake; Fowke, Keith R.

doi:10.1038/mi.2012.7

Cited by 112 publications

(122 citation statements)

References 39 publications

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“…Furthermore, local immune activation in the ectocervix of the HIV + women was shown by upregulated cellular markers and cytokine expression. Many studies have described CD4 cell subpopulations and inflammatory markers in cervical mononuclear cell preparations and in cervi- covaginal secretions of HIV + women (12,21,(31)(32)(33). However, this is, to our knowledge, the first report of expression in situ of these immune markers in genital tissues of HIV + women.…”

Section: Discussionmentioning

confidence: 53%

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

Hirbod

Kimani

Tjernlund

et al. 2013

The Journal of Immunology

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Studies using genital tissue samples from HIV-infected women might provide important information about HIV susceptibility and transmission. In this study, ectocervical biopsies were obtained from 20 HIV-seropositive (HIV+) Kenyan female sex workers (FSW) and 20 HIV-seronegative lower risk (HIV− LR) women. To control for the impact of sex work, 20 HIV− FSW were also recruited. Immune molecules were assessed in situ by immunohistochemistry and for mRNA expression by quantitative PCR. The HIV+ women were reportedly infected for a median of 3 y (1–21 y), with a median viral load of 11,735 copies/ml (20–648,000 copies/ml). These women had significantly lower CD4 blood cell counts than the HIV− LR women but comparable levels of CD4 expression in ectocervix. Whereas cellular markers were similar between the HIV+ group and the HIV− LR women, the HIV-binding molecules CCR5, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as the inflammatory markers CD69, IFN-γ, IL-6, and IL-22 were significantly upregulated in the HIV+ group. As compared with the HIV− FSW women, the HIV+ women had significantly upregulated levels of CD4, CD3, CCR5, Langerin, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as inflammatory cytokines. The CD4 cell depletion previously seen in the gut mucosa of HIV-infected individuals was thus not observed in the ectocervical mucosa. Stable CD4 cell expression and local immune activation in the lower female genital tract may promote viral replication and genital shedding and increase the risk of sexual HIV transmission.

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Section: Discussionmentioning

confidence: 53%

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

Hirbod

Kimani

Tjernlund

et al. 2013

The Journal of Immunology

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“…In a cohort of commercial sex workers, an increased level of microphage inflammatory protein-1a (MIP-1a) and microphage inflammatory protein-1b (MIP-1b) in HESN versus control groups was detected. 17 Similarly, in a serodiscordant couples cohort, in vitro secretion of beta chemokines has been shown to be higher in exposed seronegative individuals, both at baseline and upon stimulation with p24. 18 Furthermore, beta chemokines have been shown to protect CD4 + T cells from HIV-1 infection by binding to CCR5, the coreceptor for HIV-1 entry.…”

Section: Introductionmentioning

confidence: 96%

Differential Regulatory T Cell Activity in HIV Type 1-Exposed Seronegative Individuals

Pattacini

Murnane

Kahle

et al. 2013

AIDS Research and Human Retroviruses

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The potential role of conventional and regulatory T cells (Tregs) in protection from HIV-1 infection remains unclear. To address this question, we analyzed samples from 129 HIV-1-exposed seronegative individuals (HESN) from an HIV-1-serodiscordant couples cohort. To assess the presence of HIV-specific T cell responses and Treg function, we measured the proliferation of T cells in response to HIV-1 peptide pools in peripheral blood mononuclear cells (PBMCs) and PBMCs depleted of Tregs. We identified HIV-specific CD4(+) and CD8(+) T cell responses and, surprisingly, the overall CD4(+) and CD8(+) T cell response rate was not increased when Tregs were removed from cell preparations. Of the 20 individuals that had HIV-1-specific CD4(+) T cell responses, only eight had Tregs that could suppress this proliferation. When compared with individuals whose Tregs could suppress HIV-1-specific CD4(+) T cell proliferation, individuals with Tregs unable to suppress showed a trend toward increased T cell activation and Treg frequency and a significant increase in HIV-1-specific production of microphage inflammatory protein-1β (MIP-1β) by CD4(+) T cells, autocrine production of which has been shown to be protective in terms of HIV-1 infection of CD4(+) T cells.

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“…A number of studies have examined immune activation in HIV-exposed but uninfected individuals. The majority of these studies support the idea that low levels of immune activation at the time of exposure reduce the risk of HIV-1 infection (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, one recent study indicated that condom use was associated with lower levels of immune activation, potentially confounding some of the prior results (10).…”

mentioning

confidence: 73%

Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type 1 Superinfection

Blish¹,

Oc²,

Jaoko³

et al. 2014

J Virol

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fWe performed a case-control study of women at risk of HIV-1 superinfection to understand the relationship between immune activation and HIV-1 acquisition. An increase in the frequency of HIV-1 target cells, but not in other markers of T cell activation, was associated with a 1.7-fold increase in the odds of superinfection. This suggests that HIV-1 acquisition risk is influenced more by the frequency of target cells than by the generalized level of immune activation.

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A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers

Cited by 112 publications

References 39 publications

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

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

Differential Regulatory T Cell Activity in HIV Type 1-Exposed Seronegative Individuals

Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type 1 Superinfection

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