A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-11-12 DOI:10.1016/j.celrep.2024.114974

Bodie Curren, Tufael Ahmed, Ridwan B Rashid, Ismail Sebina, Md Al Amin Sikder, Daniel R Howard, Mariah Alorro, Md Ashik Ullah, Alec Bissell, Muhammed Mahfuzur Rahman, Michael A Pearen, Grant A Ramm, Antiopi Varelias, Stefan Rose-John, Kelli P A MacDonald, Robert Hoelzle, Páraic Ó Cuív, Kirsten M Spann, Paul G Dennis, Simon Phipps

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引用次数: 0

Abstract

A poor maternal diet during pregnancy predisposes the infant to severe lower respiratory tract infections (sLRIs), which, in turn, increases childhood asthma risk; however, the underlying mechanisms remain poorly understood. Here, we show that the offspring of high-fat diet (HFD)-fed mothers (HFD-reared pups) developed an sLRI following pneumovirus inoculation in early life and subsequent asthma in later life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyperneutropoiesis in the liver and elevated inflammatory cytokine expression, most notably granulocyte-colony stimulating factor (G-CSF), interleukin-17A (IL-17A), IL-6 and soluble IL-6 receptor (sIL-6R) (indicative of IL-6 trans-signaling) in the circulation and multiple organs but most prominently the liver. Inhibition of IL-6 trans-signaling using sgp130Fc transgenic mice or via specific genetic deletion of IL-6Ra on neutrophils conferred protection against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal LGSI that predisposes to sLRI and subsequent asthma via neutrophil-mediated IL-6 trans-signaling.

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母体高脂肪饮食通过增加中性粒细胞介导的 IL-6 跨信号转导易导致婴儿肺部疾病。

孕期母体饮食不当易导致婴儿患严重下呼吸道感染（sLRIs），进而增加儿童哮喘的风险；然而，人们对其潜在机制仍知之甚少。在这里，我们发现高脂饮食（HFD）喂养的母亲的后代（HFD-reared pups）在早期接种肺炎病毒后会出现严重下呼吸道感染（sLRI），并在后期接触过敏原后出现哮喘。在感染之前，HFD饲养的幼崽会出现微生物菌群失调和低度全身性炎症（LGSI），其特征是肝脏中的中性粒细胞增多和炎性细胞因子表达量升高，最明显的是血液循环和多个器官中的粒细胞集落刺激因子（G-CSF）、白细胞介素-17A（IL-17A）、IL-6和可溶性IL-6受体（sIL-6R）（表明IL-6转信号），但最突出的是肝脏。利用 sgp130Fc 转基因小鼠或通过特异性基因敲除中性粒细胞上的 IL-6Ra 来抑制 IL-6 的跨信号传导，可保护中性粒细胞免受这两种疾病的侵袭。综上所述，我们的研究结果表明，母体高纤维食物诱导新生儿LGSI，通过中性粒细胞介导的IL-6跨信号传导，易导致sLRI和随后的哮喘。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.