IL-1α is required for T cell-driven weight loss after respiratory viral infection

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-04-01 DOI:10.1016/j.mucimm.2024.02.005
Ziyin Wang , Leah F. Cuthbertson , Chubicka Thomas , Hadijatou J Sallah , Lucy G. Mosscrop , Haoyuan Li , Tiina Talts , Kartik Kumar , Miriam F. Moffatt , John S. Tregoning
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Abstract

Respiratory viral infections remain a major cause of hospitalization and death worldwide. Patients with respiratory infections often lose weight. While acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection-induced weight loss, its mechanism is not yet completely understood. We utilized a model of CD 8+ T cell-driven weight loss during respiratory syncytial virus (RSV) infection to dissect the immune regulation of post-infection weight loss. Supporting previous data, bulk RNA sequencing indicated significant enrichment of the interleukin (IL)-1 signaling pathway after RSV infection. Despite increased viral load, infection-associated weight loss was significantly reduced after IL-1α (but not IL-1β) blockade. IL-1α depletion resulted in a reversal of the gut microbiota changes observed following RSV infection. Direct nasal instillation of IL-1α also caused weight loss. Of note, we detected IL-1α in the brain after either infection or nasal delivery. This was associated with changes in genes controlling appetite after RSV infection and corresponding changes in signaling molecules such as leptin and growth/differentiation factor 15. Together, these findings indicate a lung-brain-gut signaling axis for IL-1α in regulating weight loss after RSV infection.

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呼吸道病毒感染后,T 细胞驱动的体重减轻需要 IL-1α。
呼吸道病毒感染仍然是全球住院和死亡的主要原因。呼吸道感染患者通常会体重减轻。据推测,急性体重减轻是一种限制病原体生长的耐受机制,而感染后严重的体重减轻会导致生活质量下降。尽管呼吸道感染引起的体重减轻与临床相关,但其机制尚未完全明了。我们利用呼吸道合胞病毒(RSV)感染期间 CD8+ T 细胞驱动的体重减轻模型来剖析感染后体重减轻的免疫调节。大量 RNASeq 研究表明,RSV 感染后 IL-1 信号通路显著富集,这与之前的数据相吻合。尽管病毒载量增加,但阻断IL-1α(而非IL-1β)后,感染相关的体重下降明显减少。抑制IL-1α可逆转RSV感染后观察到的肠道微生物群变化。直接从鼻腔灌入IL-1α也会导致体重下降。值得注意的是,无论是感染还是鼻腔灌注,我们都在大脑中检测到了IL-1α。这与 RSV 感染后控制食欲基因的变化以及瘦素和 GDF15 等信号分子的相应变化有关。这些发现共同表明,IL-1α在调节RSV感染后体重减轻的过程中起着肺-脑-肠信号轴的作用。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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