小柯机器人

美国国立卫生研究院Daniel C. Douek等研究人员合作发现，易位的微生物组构成可决定治疗HIV感染的免疫学结局。这一研究成果于2021年7月7日在线发表在国际学术期刊《细胞》上。

研究人员表示，尽管联合抗逆转录病毒疗法（cART）在治疗HIV感染方面取得了巨大进展，但与未感染者相比，接受治疗的HIV感染者的非艾滋病发病率和死亡率仍然较高。

在cART启动后的两年内，研究人员检测到易位微生物成分的快速、动态变化。一种无偏倚的系统生物学方法揭示了两种不同的途径，这些途径是由沙雷氏菌与其他细菌属丰度比的变化驱动的。第一年CD4 T细胞数量增加与高沙雷氏菌丰度、促炎先天细胞因子和代谢物有关，这些代谢物驱动Th17基因表达特征和粘膜完整性的恢复。随后，沙雷氏菌丰度的降低和先天细胞因子的下调允许重建全身性T细胞稳态，促进Th1和Th2基因表达特征的恢复。

对其他三个地理上不同的HIV感染队列的分析建立了一个更普遍的原则，即易位微生物物种的多样性和组成的变化会影响全身炎症，从而影响CD4 T细胞的恢复。

附：英文原文

Title: Translocated microbiome composition determines immunological outcome in treated HIV infection

Author: Krystelle Nganou-Makamdop, Aarthi Talla, Ashish Arunkumar Sharma, Sam Darko, Amy Ransier, Farida Laboune, Jeffrey G. Chipman, Gregory J. Beilman, Torfi Hoskuldsson, Slim Fourati, Thomas E. Schmidt, Sahaana Arumugam, Noemia S. Lima, Damee Moon, Samuel Callisto, Jordan Schoephoerster, Jeffery Tomalka, Peter Mugyenyi, Francis Ssali, Proscovia Muloma, Patrick Ssengendo, Ana R. Leda, Ryan K. Cheu, Jacob K. Flynn, Antigoni Morou, Elsa Brunet-Ratnasingham, Benigno Rodriguez, Michael M. Lederman, Daniel E. Kaufmann, Nichole R. Klatt, Cissy Kityo, Jason M. Brenchley, Timothy W. Schacker, Rafick P. Sekaly, Daniel C. Douek

Issue&Volume: 2021-07-07

Abstract: The impact of the microbiome on HIV disease is widely acknowledged although the mechanismsdownstream of fluctuations in microbial composition remain speculative. We detectedrapid, dynamic changes in translocated microbial constituents during two years aftercART initiation. An unbiased systems biology approach revealed two distinct pathwaysdriven by changes in the abundance ratio of Serratia to other bacterial genera. Increased CD4 T cell numbers over the first year wereassociated with high Serratia abundance, pro-inflammatory innate cytokines, and metabolites that drive Th17 geneexpression signatures and restoration of mucosal integrity. Subsequently, decreasedSerratia abundance and downregulation of innate cytokines allowed re-establishment of systemicT cell homeostasis promoting restoration of Th1 and Th2 gene expression signatures.Analyses of three other geographically distinct cohorts of treated HIV infection establisheda more generalized principle that changes in diversity and composition of translocatedmicrobial species influence systemic inflammation and consequently CD4 T cell recovery.

DOI: 10.1016/j.cell.2021.05.023

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00653-X