Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses.
Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses.
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杜氏利什曼原虫感染抑制单核细胞和巨噬细胞中的同种异体移植物炎症因子-1以抑制炎症反应。
DOI：
10.1038/s41598-020-79068-6
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发表时间：
2021-01-13
影响因子：
4.6
通讯作者：
Lipscomb MW
中科院分区：
文献类型：
--
作者：
da Silva RL;Elizondo DM;Brandy NZD;Haddock NL;Boddie TA;de Oliveira LL;de Jesus AR;de Almeida RP;de Moura TR;Lipscomb MW
巨噬细胞和单核细胞对于清除利什曼原虫感染很重要。然而，寄生虫采用的免疫逃避策略导致抑制的炎症反应，其特征在于巨噬细胞功能缺陷和单核细胞积累增加。这导致清除寄生虫负荷的能力无效。同种异体移植物炎性因子-1（AIF 1）在骨髓细胞中表达，并用于促进免疫反应。然而，在寄生虫感染期间，AIF 1参与单核细胞和巨噬细胞功能尚未被探索。这项研究现在表明，杜氏利什曼原虫抑制巨噬细胞中的AIF 1表达，以阻断促炎反应。用寄生虫攻击的小鼠脾巨噬细胞中的AIF 1表达显著降低。采用体外方法的后续研究证实，L。巨噬细胞中的donovani感染抑制AIF 1表达，这与促炎细胞因子产生的减少和寄生虫负荷的增加相关。AIF 1在巨噬细胞中的异位过表达提供了免受感染的保护，其特征在于强大的促炎细胞因子产生和有效的病原体清除。进一步的研究发现，抑制骨髓细胞或单核细胞中的AIF 1表达会损害向功能性巨噬细胞的分化。总的来说，结果表明AIF 1是控制单核细胞和巨噬细胞免疫功能的关键调节组分，并且L。donovani感染可以抑制该基因作为一种免疫逃避策略。
Macrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.
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影响因子：
7.3
作者：
Lima MHF;Sacramento LA;Quirino GFS;Ferreira MD;Benevides L;Santana AKM;Cunha FQ;Almeida RP;Silva JS;Carregaro V
通讯作者：
Carregaro V
影响因子：
3.1
作者：
Coterell, SEJ;Engwerda, CR;Kaye, PM
通讯作者：
Kaye, PM
影响因子：
3.8
作者：
Silva RL;Santos MB;Almeida PL;Barros TS;Magalhães L;Cazzaniga RA;Souza PR;Luz NF;França-Costa J;Borges VM;Lima-Junior DS;Lipscomb MW;Duthie MS;Reed SG;Almeida RP;Jesus AR
通讯作者：
Jesus AR
影响因子：
6.7
作者：
Muraille E;Gounon P;Cazareth J;Hoebeke J;Lippuner C;Davalos-Misslitz A;Aebischer T;Muller S;Glaichenhaus N;Mougneau E
通讯作者：
Mougneau E
影响因子：
6.7
作者：
Mock DJ;Hollenbaugh JA;Daddacha W;Overstreet MG;Lazarski CA;Fowell DJ;Kim B
通讯作者：
Kim B