Obesity dysregulates the pulmonary antiviral immune response.
Obesity dysregulates the pulmonary antiviral immune response.
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DOI：
10.1038/s41467-023-42432-x
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发表时间：
2023-10-19
影响因子：
16.6
通讯作者：
Singanayagam, Aran
中科院分区：
文献类型：
--
作者：
Almond, Mark;Farne, Hugo A.;Jackson, Millie M.;Jha, Akhilesh;Katsoulis, Orestis;Pitts, Oliver;Tunstall, Tanushree;Regis, Eteri;Dunning, Jake;Byrne, Adam J.;Mallia, Patrick;Kon, Onn Min;Saunders, Ken A.;Simpson, Karen D.;Snelgrove, Robert J.;Openshaw, Peter J. M.;Edwards, Michael R.;Barclay, Wendy S.;Heaney, Liam M.;Johnston, Sebastian L.;Singanayagam, Aran
肥胖是严重流感感染的一个公认的危险因素，但对易感性的潜在机制知之甚少。在这里，我们发现肥胖个体在支气管肺泡灌洗液细胞中有肺抗病毒免疫应答缺陷，但在支气管上皮细胞或外周血树突状细胞中没有。我们发现，肥胖的人气道代谢组与气道脂肪因子瘦素浓度的增加相关，这与体外抗病毒反应的幅度呈负相关。外源性肺瘦素给药直接损害体内和体外培养的气道巨噬细胞的抗病毒I型干扰素反应。因流感住院的肥胖个体表现出上呼吸道免疫反应失调。这些研究提供了对肥胖者严重流感感染倾向的驱动机制的深入了解，并提高了开发瘦素操纵或干扰素给药作为保护肥胖高危个体免受严重感染的新策略的潜力。肥胖是严重流感感染的危险因素。Almond等人指出，易感性的增加是由于气道中瘦素激素浓度的增加，瘦素抑制干扰素反应并促进严重感染。
Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals. Obesity is a risk factor for severe influenza infection. Here, Almond et al show that increased susceptibility is due to increased airway concentrations of the hormone leptin which dampens interferon responses and facilitates severe infection.
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影响因子：
2.6
作者：
Fontana, Luigi;Eagon, J. Christopher;Klein, Samuel
通讯作者：
Klein, Samuel
DOI：
10.1084/jem.20140825
发表时间：
2015-05-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goritzka M;Makris S;Kausar F;Durant LR;Pereira C;Kumagai Y;Culley FJ;Mack M;Akira S;Johansson C
通讯作者：
Johansson C
影响因子：
64.8
作者：
Minokoshi, Y;Kim, YB;Kahn, BB
通讯作者：
Kahn, BB
影响因子：
6.9
作者：
Gaur, Pratibha;Riehn, Mathias;Wirth, Dagmar
通讯作者：
Wirth, Dagmar
影响因子：
3.7
作者：
Morgan OW;Bramley A;Fowlkes A;Freedman DS;Taylor TH;Gargiullo P;Belay B;Jain S;Cox C;Kamimoto L;Fiore A;Finelli L;Olsen SJ;Fry AM
通讯作者：
Fry AM