W increased levels of IL-8, IL-1a, IL-6, TNF-a and RANTES

W increased levels of IL-8, IL-1a, IL-6, TNF-a and RANTES although these increases are not found in all studies. The genital microbiota also affects susceptibility of women to HIV heterosexual transmission, as HIV acquisition is enhanced by the presence BV [3,4,6,10?2]. BV associated inflammation is initiated by the innate immune system after bacterial products bind Toll-like receptors [11,13]. Ligand binding to the TLRs results in signaling through MYD88 or TRIF that in turn activates the rapid acting transcription factor, NF-kB. Activated NFkBdrives transcription of cytokine and adhesion molecule genes, dramatically GF120918 enhancing expression levels and activating T cells. The infiltrates of activated CCR5+ CD4+ T cells and dendritic cells in the genital mucosa of women with BV and HSV-2 [14?0] provide more target cells for HIV infection. The SIV/rhesus macaque system is a well-developed animal model that can be used for understanding the effects of genital inflammation on HIV transmission. In this animal model the phenotypic and genotypic nature of the virus inoculum is defined, the timing of the virus exposures is known and the genetics (MHC1 haplotype, TRIM5a SB-497115GR cost polymorphisms) of the animals can be defined. The vaginal microbiota of 2 populations of captive macaques was described in recent NexGen microbiome studies and, compared to humans, macaques have a relatively diverse microbiome although the most prevalent genera are those found in humans with BV [21,22]. As vaginal transmission experiments in rhesus macaques could be affected by this BV-like flora, we investigated the relationship between the vaginal microbiota and the levels of several soluble proinflammatory mediators in rhesus macaques (RM).Cervicovaginal Inflammation in Rhesus MacaquesFigure 1. Concentration of all mRNAs (relative to GAPDH) 23977191 in vaginal secretions collected between menstrual cycle days 10?0 from 36 RM at Time point 1 (March 2011) and from 30?5 RM at Time point 2 (November 2011). The samples collected at Time point 2 are denoted by the notation “22”. All vaginal secretions were collected between menstrual cycle days 10?0. Note that there was not enough CVS sample at Time point 2 to assess all mRNA targets that were tested at Time point 1. Grey bars denote median and interquartile range of the values. doi:10.1371/journal.pone.0052992.gBased on mRNA and protein levels of proinflammatory cytokines and chemokines in cervicovaginal secretions (CVS), we found that the degree of cervicovaginal inflammation in captive RM spans a broad range from minimal to severe. Further we found that the level of genital inflammation, as judged by mRNA levels of cytokines in CVS, in individual animals was relatively stable in 2 samples collected 8-months apart. In an effort to explain this inflammation, we characterized the vaginal microbiome of the animals and found that the microbiota was relatively diverse and Lactobacillus was relatively rare. Many of the macaques had similar microbiome patterns at the two time points, examined. However, we found no correlation between specific bacterial genera and the mRNA or protein levels of the inflammatory mediators in the genital tract of RM in this initial study.stainless steel wire-bottomed cages and provided with a commercial primate diet. Fresh fruit was provided once daily and water was freely available at all times.AnimalsThe 36 animals used in this study were captive-bred, parous, cycling female rhesus macaques (Macaca mulatta) from the.W increased levels of IL-8, IL-1a, IL-6, TNF-a and RANTES although these increases are not found in all studies. The genital microbiota also affects susceptibility of women to HIV heterosexual transmission, as HIV acquisition is enhanced by the presence BV [3,4,6,10?2]. BV associated inflammation is initiated by the innate immune system after bacterial products bind Toll-like receptors [11,13]. Ligand binding to the TLRs results in signaling through MYD88 or TRIF that in turn activates the rapid acting transcription factor, NF-kB. Activated NFkBdrives transcription of cytokine and adhesion molecule genes, dramatically enhancing expression levels and activating T cells. The infiltrates of activated CCR5+ CD4+ T cells and dendritic cells in the genital mucosa of women with BV and HSV-2 [14?0] provide more target cells for HIV infection. The SIV/rhesus macaque system is a well-developed animal model that can be used for understanding the effects of genital inflammation on HIV transmission. In this animal model the phenotypic and genotypic nature of the virus inoculum is defined, the timing of the virus exposures is known and the genetics (MHC1 haplotype, TRIM5a polymorphisms) of the animals can be defined. The vaginal microbiota of 2 populations of captive macaques was described in recent NexGen microbiome studies and, compared to humans, macaques have a relatively diverse microbiome although the most prevalent genera are those found in humans with BV [21,22]. As vaginal transmission experiments in rhesus macaques could be affected by this BV-like flora, we investigated the relationship between the vaginal microbiota and the levels of several soluble proinflammatory mediators in rhesus macaques (RM).Cervicovaginal Inflammation in Rhesus MacaquesFigure 1. Concentration of all mRNAs (relative to GAPDH) 23977191 in vaginal secretions collected between menstrual cycle days 10?0 from 36 RM at Time point 1 (March 2011) and from 30?5 RM at Time point 2 (November 2011). The samples collected at Time point 2 are denoted by the notation “22”. All vaginal secretions were collected between menstrual cycle days 10?0. Note that there was not enough CVS sample at Time point 2 to assess all mRNA targets that were tested at Time point 1. Grey bars denote median and interquartile range of the values. doi:10.1371/journal.pone.0052992.gBased on mRNA and protein levels of proinflammatory cytokines and chemokines in cervicovaginal secretions (CVS), we found that the degree of cervicovaginal inflammation in captive RM spans a broad range from minimal to severe. Further we found that the level of genital inflammation, as judged by mRNA levels of cytokines in CVS, in individual animals was relatively stable in 2 samples collected 8-months apart. In an effort to explain this inflammation, we characterized the vaginal microbiome of the animals and found that the microbiota was relatively diverse and Lactobacillus was relatively rare. Many of the macaques had similar microbiome patterns at the two time points, examined. However, we found no correlation between specific bacterial genera and the mRNA or protein levels of the inflammatory mediators in the genital tract of RM in this initial study.stainless steel wire-bottomed cages and provided with a commercial primate diet. Fresh fruit was provided once daily and water was freely available at all times.AnimalsThe 36 animals used in this study were captive-bred, parous, cycling female rhesus macaques (Macaca mulatta) from the.