Molecular and Systems Physiology Lab, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA; Gene Expression Lab, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA.
Cell Rep. 2023 Aug 29;42(8):112814. doi: 10.1016/j.celrep.2023.112814. Epub 2023 Jul 24.
Infections cause catabolism of fat and muscle stores. Traditionally, studies have focused on understanding how the innate immune system contributes to energy stores wasting, while the role of the adaptive immune system remains elusive. In the present study, we examine the role of the adaptive immune response in adipose tissue wasting and cachexia using a murine model of the chronic parasitic infection Trypanosoma brucei, the causative agent of sleeping sickness. We find that the wasting response occurs in two phases, with the first stage involving fat wasting caused by CD4+ T cell-induced anorexia and a second anorexia-independent cachectic stage that is dependent on CD8+ T cells. Fat wasting has no impact on host antibody-mediated resistance defenses or survival, while later-stage muscle wasting contributes to disease-tolerance defenses. Our work reveals a decoupling of adaptive immune-mediated resistance from the catabolic response during infection.
感染会导致脂肪和肌肉储存的分解代谢。传统上，研究集中于了解先天免疫系统如何导致能量储存消耗，而适应性免疫系统的作用仍然难以捉摸。在本研究中，我们使用慢性寄生虫感染 Trypanosoma brucei（昏睡病的病原体）的小鼠模型，研究适应性免疫反应在脂肪组织消耗和恶病质中的作用。我们发现，消耗反应分为两个阶段，第一阶段涉及由 CD4+T 细胞诱导的厌食引起的脂肪消耗，以及第二阶段与 CD8+T 细胞依赖性的、与厌食无关的恶病质阶段。脂肪消耗对宿主抗体介导的抵抗防御或存活没有影响，而后期的肌肉消耗有助于疾病耐受防御。我们的工作揭示了适应性免疫介导的抵抗与感染期间的分解代谢反应之间的脱耦。
