Generation of IL-23 producing dendritic cells (DCs) by airborne fungi regulates fungal pathogenicity via the induction of T(H)-17 responses.
Generation of IL-23 producing dendritic cells (DCs) by airborne fungi regulates fungal pathogenicity via the induction of T(H)-17 responses.
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DOI：
10.1371/journal.pone.0012955
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发表时间：
2010-09-23
期刊：
影响因子：
3.7
通讯作者：
Kontoyiannis DP
中科院分区：
文献类型：
--
作者：
Chamilos G;Ganguly D;Lande R;Gregorio J;Meller S;Goldman WE;Gilliet M;Kontoyiannis DP
产生白介素17(IL-17)的辅助性T细胞(TH-17)是一个新发现的T细胞亚群，在对多种真菌的适应性免疫中发挥重要作用。不同的空气真菌是否触发了TH-17诱导的共同信号通路，以及这种能力是否与每种真菌固有的致病行为有关，目前尚不清楚。在这里，我们表明，与主要的致病真菌(组织胞浆菌)相反，机会性真菌病原体(曲霉和根霉)在人类树突状细胞(DC)中触发一种共同的固有感知途径，导致IL-23的大量产生并驱动TH-17反应。这种反应需要真菌细胞壁多糖b-葡聚糖激活Dectin-1，这种多糖在机会性真菌的侵袭生长过程中选择性地暴露出来。值得注意的是，揭开组织胞浆突变体细胞壁中的b-葡聚糖不仅可以消除这种真菌的致病性，还可以触发诱导产生IL-23的树突状细胞。因此，暴露在真菌细胞壁中的b-葡聚糖对于IL-23/TH-17轴的诱导是必不可少的，并且可能是调节对机会性真菌而不是病原性真菌的保护性免疫的关键因素。
Interleukin-17 (IL-17) producing T helper cells (TH-17) comprise a newly recognized T cell subset with an emerging role in adaptive immunity to a variety of fungi. Whether different airborne fungi trigger a common signaling pathway for TH-17 induction, and whether this ability is related to the inherent pathogenic behavior of each fungus is currently unknown. Here we show that, as opposed to primary pathogenic fungi (Histoplasma capsulatum), opportunistic fungal pathogens (Aspergillus and Rhizopus) trigger a common innate sensing pathway in human dendritic cells (DCs) that results in robust production of IL-23 and drives TH-17 responses. This response requires activation of dectin-1 by the fungal cell wall polysaccharide b-glucan that is selectively exposed during the invasive growth of opportunistic fungi. Notably, unmasking of b-glucan in the cell wall of a mutant of Histoplasma not only abrogates the pathogenicity of this fungus, but also triggers the induction of IL-23 producing DCs. Thus, b-glucan exposure in the fungal cell wall is essential for the induction of IL-23/TH-17 axis and may represent a key factor that regulates protective immunity to opportunistic but not pathogenic fungi.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
30.5
作者：
Gringhuis, Sonja I.;den Dunnen, Jeroen;Geijtenbeek, Teunis B. H.
通讯作者：
Geijtenbeek, Teunis B. H.
影响因子：
4.4
作者：
Bozza, Silvia;Clavaud, Cecile;Romani, Luigina
通讯作者：
Romani, Luigina
影响因子：
64.8
作者：
Gross, Olaf;Gewies, Andreas;Ruland, Juergen
通讯作者：
Ruland, Juergen