IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection.
IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection.
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DOI：
10.1038/s41467-023-42918-8
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发表时间：
2023-11-03
影响因子：
16.6
通讯作者：
Quintana, Juan F.
中科院分区：
文献类型：
--
作者：
Sinton, Matthew C.;Chandrasegaran, Praveena R. G.;Capewell, Paul;Cooper, Anneli;Girard, Alex;Ogunsola, John;Perona-Wright, Georgia;Ngoyi, Dieudonne;Kuispond, Nono;Bucheton, Bruno;Camara, Mamadou;Kajimura, Shingo;Benezech, Cecile;Mabbott, Neil A.;Macleod, Annette;Quintana, Juan F.
在皮肤中，布鲁氏锥虫定植于皮下白色脂肪组织，并被认为有能力向前传播。寄生虫、脂肪组织和当地免疫系统之间的相互作用可能会导致感染布氏毛滴虫的牛和人的脂肪组织浪费和体重减轻。然而，从机理上讲，导致皮下白色脂肪组织浪费的事件并不完全清楚。在这里，我们使用几种互补的方法，包括飞行时间质量细胞术，批量和单细胞转录，以及体内遗传模型，我们证明了布氏毛滴虫感染推动了小鼠WAT中几个产生IL-17A的细胞的局部扩张，包括TH17和Vγ6+细胞。我们还表明，全球IL-17缺乏，或脂肪细胞IL-17受体的缺失，可以防止感染诱导的水分浪费和体重减轻。出乎意料的是，我们发现脂肪细胞IL-17信号的缺失导致DPP4+Pi16+间质前脂肪细胞显著积累，并增加了WAT中血管外寄生虫的数量，突显了IL-17信号在控制前脂肪细胞命运、皮下WAT动态和局部寄生虫负荷方面的关键作用。综上所述，我们的研究强调了脂肪细胞IL-17信号在控制感染反应中的中心作用，表明脂肪细胞是组织动力学和免疫反应对布氏毛滴虫感染的关键协调者。已知布鲁氏锥虫定植于皮下白色脂肪组织，与细胞场所的相互作用可能在发病机制和宿主反应中发挥关键作用。在这里，作者使用单细胞方法和活体动物模型，并展示了IL-17在慢性小鼠感染模型的脂肪组织反应和寄生虫负担中的作用。
In the skin, Trypanosoma brucei colonises the subcutaneous white adipose tissue, and is proposed to be competent for forward transmission. The interaction between parasites, adipose tissue, and the local immune system is likely to drive the adipose tissue wasting and weight loss observed in cattle and humans infected with T. brucei. However, mechanistically, events leading to subcutaneous white adipose tissue wasting are not fully understood. Here, using several complementary approaches, including mass cytometry by time of flight, bulk and single cell transcriptomics, and in vivo genetic models, we show that T. brucei infection drives local expansion of several IL-17A-producing cells in the murine WAT, including TH17 and Vγ6+ cells. We also show that global IL-17 deficiency, or deletion of the adipocyte IL-17 receptor protect from infection-induced WAT wasting and weight loss. Unexpectedly, we find that abrogation of adipocyte IL-17 signalling results in a significant accumulation of Dpp4+ Pi16+ interstitial preadipocytes and increased extravascular parasites in the WAT, highlighting a critical role for IL-17 signalling in controlling preadipocyte fate, subcutaneous WAT dynamics, and local parasite burden. Taken together, our study highlights the central role of adipocyte IL-17 signalling in controlling WAT responses to infection, suggesting that adipocytes are critical coordinators of tissue dynamics and immune responses to T. brucei infection. Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.2
作者：
Choe SS;Huh JY;Hwang IJ;Kim JI;Kim JB
通讯作者：
Kim JB
影响因子：
64.8
作者：
Enerback, S;Jacobsson, A;Kozak, LP
通讯作者：
Kozak, LP
影响因子：
48
作者：
Browaeys, Robin;Saelens, Wouter;Saeys, Yvan
通讯作者：
Saeys, Yvan