Evidence for dispensability of protein kinase R in host control of tuberculosis. Academic Article uri icon



  • 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 IFN-γ-dependent macrophage activation (Wu et al. PloS One. 2012 7:e30512). Here we show that co-treatment with IFN-γ 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 (TNF-α) and less interleukin 10 (IL-10) than seen with IFN-γ 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 IFN-γ were greater than those of C57BL/6J macrophages, PKR was not required to mediate the IFN-γ-dependent production of IL-10, RNI or TNF-α in either strain. Together the data cast doubt on PKR as a potential therapeutic target for tuberculosis.

publication date

  • February 28, 2018



  • Interferon-gamma
  • Macrophages
  • Mycobacterium tuberculosis
  • Tuberculosis
  • eIF-2 Kinase


PubMed Central ID

  • PMC6361384

Scopus Document Identifier

  • 85042541397

Digital Object Identifier (DOI)

  • 10.1002/eji.201747180

PubMed ID

  • 29436711

Additional Document Info


  • 48


  • 4