Evidence for dispensability of protein kinase R in host control of tuberculosis.
Evidence for dispensability of protein kinase R in host control of tuberculosis.
复制标题
DOI：
10.1002/eji.201747180
复制
发表时间：
2018-04
影响因子：
5.4
通讯作者：
Nathan CF
中科院分区：
文献类型：
--
作者：
Mundhra S;Bryk R;Hawryluk N;Zhang T;Jiang X;Nathan CF
Genetic deficiency of protein kinase R (PKR) in mice was reported to enhance macrophage activation in vitro in response to interferon-γ (IFNγ) and to reduce the burden of Mycobacterium tuberculosis (Mtb) in vivo (Wu et al. PloS One. 2012 7:e30512). Consistent with this, treatment of wild-type (WT) macrophages in vitro with a novel PKR inhibitor (Bryk et al., Bioorg. Med. Chem. Lett. 2011 21:4108–4114) also enhanced IFNγ–dependent macrophage activation (Wu et al. PloS One. 2012 7:e30512). Here we show that co-treatment with IFNγ and a new PKR inhibitor identified herein to be highly but not completely selective likewise induced macrophages to produce more reactive nitrogen intermediates (RNI) and tumor necrosis factor alpha (TNFα) and less interleukin 10 (IL-10) than seen with IFNγ alone. Unexpectedly, however, this new PKR inhibitor had a comparable effect on PKR-deficient macrophages. Retrospective investigation revealed that the PKR-deficient mice in Wu et al. (PloS One. 2012 7:e30512) had not been backcrossed. On comparing genetically matched PKR-deficient and WT mice, we saw no impact of PKR deficiency on macrophage activation in vitro or during the course of Mtb infection in vivo. In addition, although 129S1/SvImJ macrophage responses to IFNγ were greater than those of C57BL/6J macrophages, PKR was not required to mediate the IFNγ–dependent production of IL-10, RNI or TNFα in either strain. Together the data cast doubt on PKR as a potential therapeutic target for tuberculosis.
登录
查看更多内容
影响因子：
64.5
作者：
Dey, M;Cao, C;Dever, TE
通讯作者：
Dever, TE
影响因子：
30.3
作者：
Schulz O;Pichlmair A;Rehwinkel J;Rogers NC;Scheuner D;Kato H;Takeuchi O;Akira S;Kaufman RJ;Reis e Sousa C
通讯作者：
Reis e Sousa C
DOI：
10.4049/jimmunol.1200255
发表时间：
2012-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Desvignes L;Wolf AJ;Ernst JD
通讯作者：
Ernst JD
影响因子：
5.4
作者：
Dorhoi, Anca;Yeremeev, Vladimir;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
影响因子：
4.4
作者：
Asselin-Paturel, C;Brizard, G;Trinchieri, G
通讯作者：
Trinchieri, G