Profiling early lung immune responses in the mouse model of tuberculosis.
Profiling early lung immune responses in the mouse model of tuberculosis.
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DOI：
10.1371/journal.pone.0016161
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发表时间：
2011-01-13
期刊：
影响因子：
3.7
通讯作者：
Khader SA
中科院分区：
文献类型：
--
作者：
Kang DD;Lin Y;Moreno JR;Randall TD;Khader SA
结核病(TB)是由细胞内的结核分枝杆菌引起的，全世界每年有150多万人死于结核病。对结核病的免疫与产生干扰素γ的辅助性T细胞1型(Th1)在肺部的积累、结核分枝杆菌感染的巨噬细胞的激活和细菌生长的控制有关。然而，对于在结核分枝杆菌感染的肺中介导活化的Th1细胞积累的早期免疫反应，人们知之甚少。为了确定早期免疫介质在结核分枝杆菌感染肺中的诱导作用，我们在小鼠模型中进行了mRNA谱研究，并对感染早期的结核分枝杆菌感染肺中的免疫细胞进行了表征。我们的数据表明，在感染后第15天至第21天，参与病原体识别、炎性细胞因子表达、APC激活和Th1反应的mRNAs的诱导。这些mRNAs的诱导与结核分枝杆菌感染肺中Th1细胞的细胞积聚和髓系细胞的激活相一致。引人注目的是，我们发现了与Gr1+细胞相关的mRNAs的诱导，即中性粒细胞和炎性单核细胞，发生在第12天，并与结核分枝杆菌感染肺中Gr1+细胞的细胞积聚相一致。有趣的是，在体内，在第10-15天期间耗尽Gr1+中性粒细胞会导致第21天结核分枝杆菌感染肺中Th1细胞的积累减少，而不会影响整体保护结果。这些数据表明，Gr1+中性粒细胞的募集是导致趋化因子产生的早期事件，这些趋化因子调节Th1细胞在结核分枝杆菌感染的肺中的积累。
Tuberculosis (TB) is caused by the intracellular bacteria Mycobacterium tuberculosis, and kills more than 1.5 million people every year worldwide. Immunity to TB is associated with the accumulation of IFNγ-producing T helper cell type 1 (Th1) in the lungs, activation of M.tuberculosis-infected macrophages and control of bacterial growth. However, very little is known regarding the early immune responses that mediate accumulation of activated Th1 cells in the M.tuberculosis-infected lungs. To define the induction of early immune mediators in the M.tuberculosis-infected lung, we performed mRNA profiling studies and characterized immune cells in M.tuberculosis-infected lungs at early stages of infection in the mouse model. Our data show that induction of mRNAs involved in the recognition of pathogens, expression of inflammatory cytokines, activation of APCs and generation of Th1 responses occurs between day 15 and day 21 post infection. The induction of these mRNAs coincides with cellular accumulation of Th1 cells and activation of myeloid cells in M.tuberculosis-infected lungs. Strikingly, we show the induction of mRNAs associated with Gr1+ cells, namely neutrophils and inflammatory monocytes, takes place on day 12 and coincides with cellular accumulation of Gr1+ cells in M.tuberculosis-infected lungs. Interestingly, in vivo depletion of Gr1+ neutrophils between days 10–15 results in decreased accumulation of Th1 cells on day 21 in M.tuberculosis-infected lungs without impacting overall protective outcomes. These data suggest that the recruitment of Gr1+ neutrophils is an early event that leads to production of chemokines that regulate the accumulation of Th1 cells in the M.tuberculosis-infected lungs.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
血清淀粉样蛋白 A 通过独立于甲酰肽受体-1 的受体介导人中性粒细胞产生活性氧
影响因子：
5.5
作者：
Bjoerkman, Lena;Karlsson, Jennie;Dahlgren, Claes
通讯作者：
Dahlgren, Claes
影响因子：
5.5
作者：
Aoki, Naoko;Kimura, Yuka;Tateno, Masatoshi
通讯作者：
Tateno, Masatoshi
影响因子：
120.7
作者：
Dye, C;Scheele, S;Raviglione, RC
通讯作者：
Raviglione, RC
DOI：
10.1179/096805102125000092
发表时间：
2002-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Calkins, CM;Bensard, DD;McIntyre, RC
通讯作者：
McIntyre, RC