RESUMO
AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.
RESUMO
Aphids are infected by a series of bacteria that can help them survive on specific host plants. However, the associations between aphids and these bacteria are not clear, and the bacterial communities in many aphid species are poorly characterized. Here, we investigated the bacterial communities of cotton aphids (Aphis gossypii) on 2 representative winter host plants and transferred to 3 summer host plants by 16S rDNA sequencing using the Illumina MiSeq platform. Our results revealed that the bacterial communities varied among cotton aphids on hibiscus, cotton aphids on pomegranate, cotton aphids on cotton transferred from hibiscus, cotton aphids on muskmelon transferred from hibiscus, cotton aphids on cucumber transferred from hibiscus,. The diversity and richness of the bacterial communities were significantly higher in aphids on muskmelon and aphids on cucumber than in the other treatments. There were two main factors influencing the distribution of internal bacterial OTUs revealed by principal component analysis, including the differences among Punicaceae, Malvaceae and Cucurbitaceae. There were 28 bacterial communities with significant differences between two arbitrary treatments, which could be grouped into 6 main clusters depending on relative abundance. Moreover, our results indicated that in addition to the obligate endosymbiont Buchnera, with a dominant position (> 52%), A. gossypii also harbored 3 facultative endosymbiotic bacteria (Serratia, Arsenophonus, and Wolbachia) and 3 possibly symbiotic bacteria (Acinetobacter, Pantoea, and Flavobacterium). There were several correspondences between the symbiotic bacteria in cotton aphids and the specific host plants of the aphids. This study provides a better understanding of the interactions among symbiotic bacteria, aphids and host plants, suggesting that the selection pressure on aphid bacterial communities is likely to be exerted by the species of host plants.