The opiates are well-established immunomodulatory factors, and recent evidence suggests that mu- and delta-opioid receptor ligands alter chemokine-driven chemotactic responses through the process of heterologous desensitization. In the present report, we sought to examine the capacity of mu- and delta-opioids to modulate the function of chemokine receptors CCR5 and CXCR4, the two major human immunodeficiency virus (HIV) coreceptors. We found that the chemotactic responses to the CCR1/5 ligand CCL5/regulated on activation, normal T expressed and secreted, but not the CXCR4 ligand stromal cell-derived factor-1alpha/CXCL12 were inhibited following opioid pretreatment. Studies were performed with primary monocytes and Chinese hamster ovary cells transfected with CCR5 and the micro-opioid receptor to determine whether cross-desensitization of CCR5 was a result of receptor internalization. Using radiolabeled-binding analysis, flow cytometry, and confocal microscopy, we found that the heterologous desensitization of CCR5 was not associated with a significant degree of receptor internalization. Despite this, we found that the cross-desensitization of CCR5 by opioids was associated with a decrease in susceptibility to R5 but not X4 strains of HIV-1. Our findings are consistent with the notion that impairment of the normal signaling activity of CCR5 inhibits HIV-1 coreceptor function. These results have significant implications for our understanding of the effect of opioids on the regulation of leukocyte trafficking in inflammatory disease states and the process of coreceptor-dependent HIV-1 infection. The interference with HIV-1 uptake by heterologous desensitization of CCR5 suggests that HIV-1 interaction with this receptor is not passive but involves a signal transduction process.
Five rice paddy soils located in southwest China were selected for geochemical and microbial community analysis. These rice fields were irrigated with river water which was contaminated by Fe-S-rich acid mine drainage. Microbial communities were characterized by high-throughput sequencing, which showed 39 different phyla/groups in these samples. Among these phyla/groups, Proteobacteria was the most abundant phylum in all samples. Chloroflexi, Acidobacteria, Nitrospirae, and Bacteroidetes exhibited higher relative abundances than other phyla. A number of rare and candidate phyla were also detected. Moreover, canonical correspondence analysis suggested that pH, sulfate, and nitrate were significant factors that shaped the microbial community structure. In addition, a wide diversity of Fe- and S-related bacteria, such as GOUTA19, Shewanella, Geobacter, Desulfobacca, Thiobacillus, Desulfobacterium, and Anaeromyxobacter, might be responsible for biogeochemical Fe and S cycles in the tested rice paddy soils. Among the dominant genera, GOUTA19 and Shewanella were seldom detected in rice paddy soils.
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