加拿大多伦多大学David G. Brooks小组发现，早期的先天性和适应性免疫干扰决定慢性病毒和结核分枝杆菌共感染的长期严重程度。这一研究成果于2021年1月29日在线发表在国际学术期刊《免疫》上。

据研究人员介绍，慢性病毒感染会增加结核分枝杆菌（Mtb）合并感染的严重性。

研究人员测试了慢性病毒感染如何改变肺微环境从而促进合并感染并加重疾病的严重程度。研究人员开发了一种慢性病毒和Mtb感染的协同系统，可诱导共感染的主要临床表现，包括Mtb负担增加、肺外传播和死亡率增加。这些疾病状态不是由于慢性病毒引起的免疫抑制或衰竭所致。相反，增加的细胞因子TNFα最初阻止了肺部Mtb的生长，阻止了树突状细胞介导的抗原转运至淋巴结，并破坏了免疫监视，从而使细菌得以庇护。

隐蔽的Mtb复制延迟了CD4 T细胞的活化，使T辅助（Th）1转向Th17分化，并增加了肺中性粒细胞增多，从而降低了长期存活率。短暂恢复CD4 T细胞诱导克服了这些疾病后遗症，进而增强了对Mtb的控制。因此，Mtb从慢性炎症环境中选择TNFα来破坏免疫监视，避免早期免疫功能，并促进长期共感染。 

附：英文原文

Title: Early innate and adaptive immune perturbations determine long-term severity of chronic virus and Mycobacterium tuberculosis coinfection

Author: Wenxi Xu, Laura M. Snell, Mengdi Guo, Giselle Boukhaled, Bethany L. Macleod, Ming Li, Michael V. Tullius, Cynthia J. Guidos, Ming-Sound Tsao, Maziar Divangahi, Marcus A. Horwitz, Jun Liu, David G. Brooks

Issue&Volume: 2021-01-29

Abstract: Chronic viral infections increase severity of Mycobacterium tuberculosis (Mtb) coinfection. Here, we examined how chronic viral infections alter the pulmonarymicroenvironment to foster coinfection and worsen disease severity. We developed acoordinated system of chronic virus and Mtb infection that induced central clinical manifestations of coinfection, includingincreased Mtb burden, extra-pulmonary dissemination, and heightened mortality. These disease stateswere not due to chronic virus-induced immunosuppression or exhaustion; rather, increasedamounts of the cytokine TNFα initially arrested pulmonary Mtb growth, impeding dendritic cell mediated antigen transportation to the lymph nodeand subverting immune-surveillance, allowing bacterial sanctuary. The cryptic Mtb replication delayed CD4 T cell priming, redirecting T helper (Th) 1 toward Th17 differentiationand increasing pulmonary neutrophilia, which diminished long-term survival. Temporallyrestoring CD4 T cell induction overcame these diverse disease sequelae to enhanceMtb control. Thus, Mtb co-opts TNFα from the chronic inflammatory environment to subvert immune-surveillance,avert early immune function, and foster long-term coinfection.

DOI: 10.1016/j.immuni.2021.01.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00026-1