Aspf2 From Aspergillus fumigatus Recruits Human Immune Regulators for Immune Evasion and Cell Damage.
Aspf2 From Aspergillus fumigatus Recruits Human Immune Regulators for Immune Evasion and Cell Damage.
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DOI：
10.3389/fimmu.2018.01635
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zipfel PF
中科院分区：
文献类型：
--
作者：
Dasari P;Shopova IA;Stroe M;Wartenberg D;Martin-Dahse H;Beyersdorf N;Hortschansky P;Dietrich S;Cseresnyés Z;Figge MT;Westermann M;Skerka C;Brakhage AA;Zipfel PF
机会性真菌病原体烟曲霉会导致危及生命的感染，特别是在免疫功能低下的患者中。大多数病原微生物在最早的时候就控制了宿主的先天性免疫反应，在渗透的宿主免疫细胞到达感染部位之前就已经如此。在这里，我们确定Aspf2是第一个烟曲霉菌因子H结合蛋白。Aspf2招募了几个人类血浆调节因子，因子H，因子-H样蛋白1(FHL-1)，FHR1，和纤溶酶原。因子H通过位于SCRs6-7和SCR20的两个区域与Aspf2接触。FHL-1通过SCRs6-7结合，FHR1通过SCRs3-5结合。与Aspf2结合的因子H和FHL-1维持辅因子活性，并辅助C3b失活。产生了一株FHLASF2基因敲除株，与H因子结合的强度为28%，与Δ-1结合强度降低了42%。与免疫调节剂获得较少一致的是，当用补体活性正常人血清攻击时，Δaspf2分生孢子在其表面沉积了相当多的C3b(>；57%)。因此，与野生型分生孢子相比，Δaspf2分生孢子能更有效地被人中性粒细胞吞噬(-gt；20%)和杀灭(44%)。此外，Aspf2招募了人的纤溶酶原，当被组织型纤溶酶原激活剂激活时，新产生的纤溶酶切割发色底物S2251并降解纤维蛋白原。此外，附着在分生孢子上的纤溶酶损伤人肺上皮细胞，诱导细胞回缩，并导致基质暴露。因此，Aspf2是烟曲霉菌的中枢免疫逃避蛋白和纤溶酶原配体。通过阻止宿主的先天性免疫攻击和破坏人类肺上皮细胞层，Aspf2有助于真菌感染的早期步骤，并可能允许组织渗透。
The opportunistic fungal pathogen Aspergillus fumigatus can cause life-threatening infections, particularly in immunocompromised patients. Most pathogenic microbes control host innate immune responses at the earliest time, already before infiltrating host immune cells arrive at the site of infection. Here, we identify Aspf2 as the first A. fumigatus Factor H-binding protein. Aspf2 recruits several human plasma regulators, Factor H, factor-H-like protein 1 (FHL-1), FHR1, and plasminogen. Factor H contacts Aspf2 via two regions located in SCRs6–7 and SCR20. FHL-1 binds via SCRs6–7, and FHR1 via SCRs3–5. Factor H and FHL-1 attached to Aspf2-maintained cofactor activity and assisted in C3b inactivation. A Δaspf2 knockout strain was generated which bound Factor H with 28% and FHL-1 with 42% lower intensity. In agreement with less immune regulator acquisition, when challenged with complement-active normal human serum, Δaspf2 conidia had substantially more C3b (>57%) deposited on their surface. Consequently, Δaspf2 conidia were more efficiently phagocytosed (>20%) and killed (44%) by human neutrophils as wild-type conidia. Furthermore, Aspf2 recruited human plasminogen and, when activated by tissue-type plasminogen activator, newly generated plasmin cleaved the chromogenic substrate S2251 and degraded fibrinogen. Furthermore, plasmin attached to conidia damaged human lung epithelial cells, induced cell retraction, and caused matrix exposure. Thus, Aspf2 is a central immune evasion protein and plasminogen ligand of A. fumigatus. By blocking host innate immune attack and by disrupting human lung epithelial cell layers, Aspf2 assists in early steps of fungal infection and likely allows tissue penetration.
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影响因子：
6.7
作者：
Citiulo F;Jacobsen ID;Miramón P;Schild L;Brunke S;Zipfel P;Brock M;Hube B;Wilson D
通讯作者：
Wilson D
影响因子：
3.6
作者：
Carlsson, F;Sandin, C;Lindahl, G
通讯作者：
Lindahl, G
影响因子：
--
作者：
Amich, Jorge;Vicentefranqueira, Rocio;Antonio Calera, Jose
通讯作者：
Antonio Calera, Jose
DOI：
10.1152/ajplung.00056.2013
发表时间：
2013-08-01
影响因子：
4.9
作者：
Bartlett, Jennifer A.;Albertolle, Matthew E.;Williams, Katherine E.
通讯作者：
Williams, Katherine E.
影响因子：
3.1
作者：
Behnsen, Judith;Lessing, Franziska;Brakhage, Axel A.
通讯作者：
Brakhage, Axel A.