New recognition of Leishmania major by infected macrophages

受感染的巨噬细胞对大型利什曼原虫的新识别

• 批准号: 18590401
• 负责人: HONMA Kiri
• 金额: $ 2.57万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590401/
• 关键词: IRF-4; proinflammatory cvtokines; Leishmania major; macronhages; L.major

(A)When L.major infected to IRF-4 deficient macrophages in vivo, footpad thickness increased at the early stage (2-5 weeks after infection)compared to wild type.(B)The rate of the L.major infection was same between IRF-4 deficient macrophages and wild-type cells. However, the proportion of the infected macrophages remarkably decreased compared to wild type when L.major infected to IRF-4 deficient macrophages for 48 hrs in vitro, suggested that IRF-4 negatively regulated exclusion of L.major from the infected macrophages. TNF-α and NO from IRF-4 deficient, L.major-infected macrophages produced much higher than wild-type. Interestingly, IL-12 from IRF-4 deficient, and L.major infected macrophages produced much lower than wild-type. We expected that signaling to recognize L.major was different from TLR signaling because we have already reported that both IL-12 and TNF-α production through TLR remarkably enhanced in IRF-4 deficient macrophages. Alternation of cytokine production in IRF-4 KO macrophages to infect with L.major regulated at the transcriptional level. Various kind of denatured L.major antigens were made to identify major L.major molecule. Heat denatured or Proteinase K treated L.major antigen did not affect cytokine production pattern of TNF-α or IL-12 in IRF-4 KO macrophages. L.major molecule contained in insoluble fraction and was Proteinase K resistant molecule. It suggested that major antigen was not protein. And it was impossible to use ion exchange chromatography such as Bio-Cad.(C)To separate L.major antigen, gel filtration method have been performed because it was able to separate each molecules by molecular weight.

（A）当硕大乳杆菌体内感染IRF-4缺陷型巨噬细胞时，与野生型相比，足垫厚度在早期（感染后2-5周）增加。（B）IRF-4缺陷型巨噬细胞和野生型细胞之间的硕大利什曼原虫感染率相同。IRF-4缺陷型巨噬细胞体外感染48 h后，感染巨噬细胞的比例明显低于野生型巨噬细胞，提示IRF-4负调控巨噬细胞对感染巨噬细胞的排斥作用。IRF-4缺陷型巨噬细胞的TNF-α和NO产生量远高于野生型巨噬细胞。有趣的是，来自IRF-4缺陷型和大型乳杆菌感染的巨噬细胞的IL-12产生比野生型低得多。我们预期识别硕大乳杆菌的信号传导不同于TLR信号传导，因为我们已经报道了在IRF-4缺陷的巨噬细胞中通过TLR产生的IL-12和TNF-α显著增强。IRF-4 KO巨噬细胞中细胞因子产生的变化在转录水平上受硕大乳杆菌感染的调节。制备了各种变性的L.major抗原以鉴定L.major主要分子。热变性或蛋白酶K处理的主要军团菌抗原不影响IRF-4 KO巨噬细胞中TNF-α或IL-12的细胞因子产生模式。L.主要分子存在于不溶性组分中，为蛋白酶K抗性分子。提示主要抗原不是蛋白质。而Bio-Cad等离子交换层析法则不可能。(C)To由于凝胶过滤法能够通过分子量分离每个分子，因此已经进行了分离主要军团菌抗原的凝胶过滤法。

项目成果

IRF-4 negatively regulates cytokine production by macrophages in response to TLR.

IRF-4 响应 TLR 负调节巨噬细胞产生细胞因子。

• 发表时间: 2006
• 作者: Katsuyuki;Yui
• 通讯作者: Yui

N.brasiliensis排虫に重要なTh2サイトカイン産生におけるIRF-4の役割

IRF-4 在 Th2 细胞因子产生中的作用对于巴西猪笼草的排出很重要

• 发表时间: 2007
• 作者: S.;Yoshida;Y.;Yanagi;Y.;Yoshikai;本間 季里;本間 季里
• 通讯作者: 本間 季里

Interferon regulatory factor-4 negatively regulates IL-4 production of naive CD4 T cells

干扰素调节因子 4 负向调节初始 CD4 T 细胞的 IL-4 产生

• 发表时间: 2007
• 作者: Tetsutani;K.;et. al.;Tetsutani K et al.;Tao K et al.;Coban C et al.;Koga R et al.;Inagaki-Ohara K et al.;Ishii K et al.;本間 季里
• 通讯作者: 本間 季里

Interferon regulatory factor-4(IRF-4)negatively modulates IL-4 production from naive CD4 T cells

干扰素调节因子 4 (IRF-4) 负向调节初始 CD4 T 细胞产生 IL-4

• 发表时间: 2006
• 作者: Kiri;Honma;本間 季里;木村 大輔;Kiri Honma
• 通讯作者: Kiri Honma

The role of IRF-4 to eliminate L.major from the infected Macrophages.

IRF-4 从受感染的巨噬细胞中消除 L.major 的作用。

• 发表时间: 2005
• 作者: Kiri;Honma
• 通讯作者: Honma