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1.
Mucosal Immunol ; 10(1): 69-78, 2017 01.
Article in English | MEDLINE | ID: mdl-27049061

ABSTRACT

Invariant natural killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented by CD1d. These immunoregulatory cells have the capacity for rapid cytokine release after antigen recognition and are essential for the activation of multiple arms of the immune response. HIV-1 infection is associated with iNKT cell depletion in the peripheral blood; however, their role in the gastrointestinal-associated lymphoid tissue (GALT) is less well studied. Our results show that iNKT cells are found at a higher frequency in GALT compared with blood, particularly in HIV-1 elite controllers. The capacity of iNKT cells to produce interleukin-4 (IL-4) and IL-10 in the GALT was associated with less immune activation and lower markers of microbial translocation, whereas regulatory T cell frequency showed positive associations with immune activation. We hypothesized that the composition of the microbiota would influence iNKT cell frequency and function. We found positive associations between the abundance of several Bacteroides species and iNKT cell frequency and their capacity to produce IL-4 in the GALT but not in the blood. Overall, our results are consistent with the hypothesis that GALT iNKT cells, influenced by certain bacterial species, may have a key role in regulating immune activation in HIV-1 infection.


Subject(s)
Bacteroides/immunology , Gastrointestinal Microbiome/immunology , HIV Infections/immunology , HIV-1/immunology , Intestines/immunology , Natural Killer T-Cells/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Aged , Antigens, CD1d/metabolism , Cells, Cultured , Female , Humans , Immunity, Innate , Interleukin-10/metabolism , Interleukin-4/metabolism , Lipids/immunology , Male , Middle Aged , Natural Killer T-Cells/microbiology , Natural Killer T-Cells/virology , Young Adult
2.
Epidemiol Infect ; 144(1): 123-37, 2016 01.
Article in English | MEDLINE | ID: mdl-26062721

ABSTRACT

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.


Subject(s)
Microbiota , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Vagina/microbiology , Adolescent , Adult , Aged , DNA, Bacterial/genetics , Female , Genotype , Humans , Middle Aged , Nigeria/epidemiology , Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Prevalence , RNA, Ribosomal, 16S/genetics , Vagina/virology , Young Adult
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