These women and the CVS samples of the RM studied here, the median levels of IL-1b, IP-10 and IL-8 were 10?100 fold higher in RM CVS, the median level of IL-12p70 were 3 fold higher in RM CVS, and the median level of IL-6 was similar in the women and RM. The cytokines/chemokines that were relatively elevated in the CVS of many RM included IL-1b, IP-10 and IL-8 which are classic mediators of inflammation. IL-1b is increased in women with bacterial vaginosis compared to women with a genital microbiota dominated by Lactobacillus [9,10]. In most animals, the mRNA levels of the inflammatory 25033180 mediators were similar in the 2 CVS samples collected 8 months apart, suggesting that genital inflammation is stable in a subset of captive female RM. It seems likely similar levels of pre-existing cervicovaginal inflammation were MK 8931 present in RM used for published vaginal transmission experiments [30?7] and that this influenced the results of these experiments. The current studies of the RM genital microbiota showed several features that appear to be common to the RM and pigtailed macaques genital microbiota described in recent pyrosequencing studies [21,22]; 1) the microbiota was relatively diverse especially compared to humans with a “high-lactobacillus” microbiota; 2) there was a low frequency of Lactobacillus; 3) when Lactobacillus was present, the species were different than those found in humans; and 4) many of the more prevalent genera present in the rhesus macaques are the same as those found frequently in humans with bacterial vaginosis including Prevotella, Sneathia, Peptoniphilis and Mobiluncus. However, this study showed a notable difference with the previous microbiome studies. Thus, Porphyromonas was by far the most predominant genus in these macaques since it was present at fairly high levels in nearly all of the macaques. In contrast, while significant levels of Porphyromonas sequences were observed in the two previous studies, [21,22] the previous rhesus macaque studied had Sneathia, Mobiluncus andStreptococcus sequences at the highest levels while the pigtailed macaques had Sneathia and Fusobacterium sequences at strikingly high levels [21,22]. Thus, taken together these three studies suggest that the genital microbiota at a primate center can have a characteristic signature pattern. A striking finding was the stability of vaginal microbiota in some of the macaques. Although these animals were sampled 8 months apart, the microbiota in some of the macaques was highly similar at the two time points. However, the microbiota was in most cases very different between animals. A recent study by Gajer et al. [38] shows that microbiota in healthy
humans can be relatively stable over a 16-week period, although in most healthy women the genital microbiota was dominated by Lactobacillus. It is worth noting that the protein and mRNA levels for 2 of 3 cytokines tested in both assays did not correlate. However this is not HIV-RT inhibitor 1 site surprising given that the levels of many cytokines including IL12 and TNF are regulated at the level of post-translation modification and gene expression. Further, the degradation rates of intracellular mRNA and secreted proteins are expected to differ. expected correlations between the mRNA levels of inducer and effector molecules were often in apparent. Thus IFN-a mRNA did not correlate with mRNA levels of the ISGs Mx, OAS and IP-10. Similarly, the mRNA levels of MIG and IFN-gamma in CVS did not correlate despite the fact the IFN-.These women and the CVS samples of the RM studied here, the median levels of IL-1b, IP-10 and IL-8 were 10?100 fold higher in RM CVS, the median level of IL-12p70 were 3 fold higher in RM CVS, and the median level of IL-6 was similar in the women and RM. The cytokines/chemokines that were relatively elevated in the CVS of many RM included IL-1b, IP-10 and IL-8 which are classic mediators of inflammation. IL-1b is increased in women with bacterial vaginosis compared to women with a genital microbiota dominated by Lactobacillus [9,10]. In most animals, the mRNA levels of the inflammatory 25033180 mediators were similar in the 2 CVS samples collected 8 months apart, suggesting that genital inflammation is stable in a subset of captive female RM. It seems likely similar levels of pre-existing cervicovaginal inflammation were present in RM used for published vaginal transmission experiments [30?7] and that this influenced the results of these experiments. The current studies of the RM genital microbiota showed several features that appear to be common to the RM and pigtailed macaques genital microbiota described in recent pyrosequencing studies [21,22]; 1) the microbiota was relatively diverse especially compared to humans with a “high-lactobacillus” microbiota; 2) there was a low frequency of Lactobacillus; 3) when Lactobacillus was present, the species were different than those found in humans; and 4) many of the more prevalent genera present in the rhesus macaques are the same as those found frequently in humans with bacterial vaginosis including Prevotella, Sneathia, Peptoniphilis and Mobiluncus. However, this study showed a notable difference with the previous microbiome studies. Thus, Porphyromonas was by far the most predominant genus in these macaques since it was present at fairly high levels in nearly all of the macaques. In contrast, while significant levels of Porphyromonas sequences were observed in the two previous studies, [21,22] the previous rhesus macaque studied had Sneathia, Mobiluncus andStreptococcus sequences at the highest levels while the pigtailed macaques had Sneathia and Fusobacterium sequences at strikingly high levels [21,22]. Thus, taken together these three studies suggest that the genital microbiota at a primate center can have a characteristic signature pattern. A striking finding was the stability of vaginal microbiota in some of the macaques. Although these animals were sampled 8 months apart, the microbiota in some of the macaques was highly similar at the two time points. However, the microbiota was in most cases very different between animals. A recent study by Gajer et al. [38] shows that microbiota in healthy humans can be relatively stable over a 16-week period, although in most healthy women the genital microbiota was dominated by Lactobacillus. It is worth noting that the protein and mRNA levels for 2 of 3 cytokines tested in both assays did not correlate. However this is not surprising given that the levels of many cytokines including IL12 and TNF are regulated at the level of post-translation modification and gene expression. Further, the degradation rates of intracellular mRNA and secreted proteins are expected to differ. expected correlations between the mRNA levels of inducer and effector molecules were often in apparent. Thus IFN-a mRNA did not correlate with mRNA levels of the ISGs Mx, OAS and IP-10. Similarly, the mRNA levels of MIG and IFN-gamma in CVS did not correlate despite the fact the IFN-.