Vaginal IL-8 levels are positively associated with Candida albicans and inversely with lactobacilli in HIV-infected women

Spear, Gregory T.; Zariffard, M. Reza; Cohen, Mardge H.; Sha, Beverly E.

doi:10.1016/j.jri.2007.11.001

Cited by 34 publications

(24 citation statements)

References 15 publications

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“…We now demonstrate for the first time using an expanded panel of innate immunity mediators that this immuno-modulatory phenomenon is also true for the L. jensenii isolate 1153 and its bioengineered derivatives. The results of our study agree with clinical observations showing an association of vaginal lactobacilli with relatively low levels of pro-inflammatory mediators in-vivo [56-58]. Furthermore, the results from our in-vitro model are in agreement with findings generated in a macaque model of SHIV infection [26].…”

Section: Discussionsupporting

confidence: 91%

Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide

Yamamoto

Fichorova

2013

BMC Microbiol

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BackgroundVaginal probiotics are investigated as a binary strategy for prevention of bacterial vaginosis and HIV. We applied an innovative experimental model using primary and immortalized human cervical and vaginal epithelial cells to assess the functional properties of Lactobacillus jensenii, a predominant constituent of the healthy vaginal microbiome, engineered to express the HIV-1 entry inhibitor modified cyanovirin-N (mCV-N). In this model bacteria colonize the epithelial cells over a period of 24-72 h. Staurosporine and the Toll-like receptor 2/6 ligand macrophage-activating lipopeptide-2 (MALP-2) serve as positive controls for apoptosis and proinflammatory activation, respectively. In 24-hour intervals, the colonized epithelium is assessed microscopically, supernatants are collected for measurement of soluble immunoinflammatory mediators and production of CV-N, and cells are lysed for assessment of: 1) apoptosis by cleaved versus total caspase-3 assay; 2) NF-κB activation by a luciferase reporter assay; or 3) epithelia-associated colony forming units (CFU) in Brucella agar.ResultsWild type (WT) L. jensenii 1153 consistently colonized cervical and vaginal cells in the absence of epithelial damage and apoptosis. The bioengineered derivatives expressing mCV-N or control plasmids showed the same stable colonization pattern, which was reproducible between technologists and bacterial batches (CFU coefficient of variation <10% within and between experiments and epithelial cell types). MALP-2 activated NF-κB and caused fold-increased levels of proinflammatory mediators with clinically established significance in the cervicovaginal environment (IL-1α, IL-1β, IL-6, TNF-α, IL-8, RANTES, MIP-3α, and ICAM-1), measured by a multiplex electrochemiluminescence assay. At the same time levels of protective anti-inflammatory mediators interleukin 1 receptor antagonist (IL-1RA) and secretory leukocyte protease inhibitor (SLPI), both measured by ELISA, remained constant (IL-1RA) or moderately increased (SLPI). Similarly to MALP-2, colonization by L. jensenii WT activated NF-κB; however, unlike the synthetic TLR2/6 ligand, the live microorganisms did not induce significant changes in the secreted levels across all inflammation-associated proteins. The mCV-N production and function were confirmed by western blot and a HIV-1 gp120 binding assay, respectively. The bioengineered lactobacilli expressed mCV-N with anti-HIV activity preserved in the epithelial cell context and caused no significant immunoinflammatory changes as compared to the WT L. jensenii.ConclusionsThese results highlight the translational value of the colonization model and justify further clinical investigation of the homeostatic and anti-HIV effectiveness of the L. jensenii derivates.

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Section: Discussionsupporting

confidence: 91%

Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide

Yamamoto

Fichorova

2013

BMC Microbiol

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“…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.…”

Section: Discussionmentioning

confidence: 96%

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

Mitchell

Balkus

McKernan-Mullin

et al. 2013

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Cervical shedding of HIV-1 DNA may influence HIV-1 sexual transmission. HIV-1 DNA was detected in 250/316 (80%) and 207/259 (79%) cervical cytobrush specimens from 56 United States (US) and 80 Kenyan women, respectively. Plasma HIV-1 RNA concentration was associated with increased HIV-1 DNA shedding among US and Kenyan women. Kenyan women had higher cervicovaginal concentrations of pro-inflammatory interleukins (IL)-1β, IL-6, IL-8 and anti-inflammatory secretory leukocyte protease inhibitor (SLPI) compared to US women (all p < 0.01). HIV-1 DNA shedding was associated with increased concentrations of IL-1β and IL-6 and lower SLPI among US women, but not Kenyan women.

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“…25 Several groups have shown that local, genital markers of inflammation are associated with increased HIV-1 genital shedding. 12,15 Anderson et al showed that the presence of white blood cells in CVL is associated with increased detection of HIV-1 in CVL, even after controlling for plasma viral load, 26 but did not control for the presence of genital coinfections. Higher rates of genital shedding of HIV-1 are seen in women with concomitant genital tract infections such as herpes 27 or BV.…”

Section: Discussionmentioning

confidence: 99%

“…Proinflammatory cytokines such as interleukin (IL)-1b, tumor necrosis factor (TNF)-a, IL-6, and IL-8 are increased in many genital infections [10][11][12][13] and with genital shedding of HIV-1. [14][15][16] Vaginal hygiene practices 17 and cryotherapy for cervical neoplasia 18 have also been associated with genital HIV-1 shedding, which many hypothesize is related to inflammation resulting from trauma to vaginal epithelium.…”

Section: Introductionmentioning

confidence: 99%

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

Mitchell

Hitti

Paul

et al. 2011

AIDS Research and Human Retroviruses

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We examined the relationship of proinflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital coinfections. Fifty-seven HIV-1-infected women in Seattle, WA (n = 38) and Rochester, NY (n = 19) were followed every 3-4 months for a total of 391 visits. At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using qPCR. Vaginal samples were tested for bacterial vaginosis, yeast, hydrogen peroxide-producing Lactobacillus colonization, Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, CMV, and HSV shedding. CVL interleukins (IL)-1β, IL-6, IL-8, and SLPI were measured using ELISA. Linear regression with generalized estimating equations examined effects of cytokine concentrations on CVL HIV-1 RNA, adjusted for plasma HIV RNA, and measured coinfections. CVL IL-1β and IL-8 were significantly associated with CVL HIV-1 RNA. This persisted after adjusting for plasma HIV-1 RNA. Higher levels of IL-1β were associated with higher concentrations of HIV-1 RNA in CVL (β = 0.25, 95% CI 0.09, 0.42), as were higher levels of IL-8 (β = 0.34, 95% CI 0.17, 0.50). Adjusting for the presence of the coinfections described, this relationship was attenuated for IL-1β (β = 0.16; 95% CI -0.01, 0.33) but still significant for IL-8 (β = 0.29; 95% CI 0.13, 0.45). The proinflammatory cytokines IL-1β and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, even after controlling for plasma viral load and vaginal microbial cofactors. This association suggests that there may be additional, noninfectious causes of inflammation that increase cervicovaginal HIV-1 shedding.

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Vaginal IL-8 levels are positively associated with Candida albicans and inversely with lactobacilli in HIV-infected women

Cited by 34 publications

References 15 publications

Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide

Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide

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

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

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