Increased interleukin-10 in the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission?

Cohen, Craig R.; Plummer, Francis A.; Mugo, Nelly; Maclean, Ian; Shen, Caixia; Bukusi, Elizabeth A.; Irungu, Elizabeth; Sinei, Samuel; Bwayo, Job J.; Brunham, Robert C.

doi:10.1097/00002030-199902250-00004

Cited by 103 publications

(61 citation statements)

References 26 publications

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“…So far, cervical explant assays are only set up in a pre-clinical studies context and many caveats (clinical history, hormonal status, ectocervix or endocervix, exposure to local products) have been identified. 31 In a controlled trial setting, at least the clinical background will be fully described. Furthermore, it is questionable if the low statistical power due to the limited number of biopsies per participant can lead to meaningful results.…”

Section: Discussionmentioning

confidence: 99%

“…31,32 The presence of these pathogens may confound the relationship between an experimental medication or vaccine and the local immune 24,33 Serum or urine samples for endogenous hormones should be collected and menstrual phase applied to the analysis of results. Finally, vitamin D is an important immune modulator, can be tested in serum and considered as a confounder.…”

Section: Confoundersmentioning

confidence: 99%

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Methodological Issues in Sampling the Local Immune System of the Female Genital Tract in the Context of HIV Prevention Trials

Jespers

Francis

Wijgert

et al. 2010

American J Rep Immunol

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Citation  Jespers V, Francis SC, van de Wijgert J, Crucitti T. Methodological issues in sampling the local immune system of the female genital tract in the context of HIV prevention trials. Am J Reprod Immunol 2011; 65: 368–376 The spread of HIV continues unabated in the most vulnerable populations of the world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine, pre‐exposure prophylaxis or a vaccine, are urgently needed in the fight against new infections. We must make a commitment to supporting innovative research and product design, so that one or more of these products provide a halt to the spread of HIV. Above all, these products should be proven to be safe and not negatively disturb the local immune system in a way that facilitates or enhances heterosexual transmission of HIV. HIV specific and non specific cellular and humoral local vaginal immunity must be assessed in clinical trials when testing prevention products for safety or efficacy. A proven, well‐documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune responses. In this paper, we will discuss methods for vaginal immunology sampling in the context of clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Confoundersmentioning

confidence: 99%

Methodological Issues in Sampling the Local Immune System of the Female Genital Tract in the Context of HIV Prevention Trials

Jespers

Francis

Wijgert

et al. 2010

American J Rep Immunol

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“…Although IL-12 has been consistently found to be associated with protection (28, 40), higher IL-10 production has been previously linked to susceptibility to C. trachomatis infection and immunopathology in mouse and human chlamydial diseases (17,47,49). It remains unclear why a DC subset, which produces higher levels of these two apparently functionally counteractive cytokines, showed dominant protective phenotype.…”

Section: Discussionmentioning

confidence: 99%

Adoptive Transfer of CD8α+ Dendritic Cells (DC) Isolated from Mice Infected with Chlamydia muridarum Are More Potent in Inducing Protective Immunity Than CD8α− DC

Bilenki

Wang

Yang

et al. 2006

The Journal of Immunology

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Chlamydial infections are serious public health concerns worldwide. In this study, we examined the role of dendritic cell (DC) subsets in inducing protective immunity against chlamydial infection using an adoptive transfer approach. We found that CD11c+CD8α+ (double-positive, DP) DC, compared with CD11c+CD8α− (single-positive, SP) DC isolated from infected mice, are more potent inducers of protective immunity. Specifically, mice pretreated with DPDC from infected mice, upon infection with Chlamydia trachomatis mouse pneumonitis (MoPn), experienced significantly less severe body weight loss and in vivo chlamydial growth. Analysis of MoPn-driven cytokine production by immune cells revealed that mice that were treated with DPDC produced significantly higher levels of Th1 (TNF-α, IFN-γ, and IL-12) but lower levels of Th2 (IL-4, IL-5, and IL-13)-related cytokines than the recipients of SPDC following infection challenge. Moreover, DPDC-treated mice displayed significantly higher levels of MoPn-specific IgG2a production and delayed-type hypersensitivity responses compared with SPDC-treated mice. Furthermore, DPDC isolated from infected mice produced higher amounts of IL-12 and IL-10 in vitro in comparison with SPDC. These data indicate that CD8α+ DC have a significantly higher capacity in inducing protective immunity compared with CD8α− DC, demonstrating the crucial role of DC1-like cells in eliciting protection against C. trachomatis infection

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“…15 It has been thought that increased production of IL10 confers risk of severe disease by antagonism of the Th1 response necessary for clearance of chlamydial infection. 10,11 However, IL10 produced locally by T lymphocytes and antigen-presenting cells antagonises the proinflammatory response, and consequent reduced tissue remodelling 55,56 in the inflamed conjunctiva might explain why more efficient IL10 production might have a beneficial effect on the risk of adverse outcomes in trachoma. In the ongoing work, we are studying the functional significance of the above associations by quantifying IL10 haplotype-specific transcription in vivo and investigate whether any of the differences found are due to functional SNPs within the risk or protective haplotypes.…”

Section: Discussionmentioning

confidence: 99%

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

et al. 2005

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Experimental evidence implicates interferon gamma (IFNg) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNg loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNg SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNg and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNg þ 874A allele, previously linked to lower IFNg production, lies in the IFNg risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.

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Increased interleukin-10 in the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission?

Abstract: The association of non-ulcerative STD and bacterial vaginosis with increased frequency of IL-10 detection in endocervical secretions suggests a potential mechanism through which these infections may alter susceptibility to HIV-1 infection in women.

Cited by 103 publications

References 26 publications

Methodological Issues in Sampling the Local Immune System of the Female Genital Tract in the Context of HIV Prevention Trials

Methodological Issues in Sampling the Local Immune System of the Female Genital Tract in the Context of HIV Prevention Trials

Adoptive Transfer of CD8α+ Dendritic Cells (DC) Isolated from Mice Infected with Chlamydia muridarum Are More Potent in Inducing Protective Immunity Than CD8α− DC

Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci

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