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Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii.

Publication ,  Journal Article
Dockterman, J; Fee, BE; Taylor, GA; Coers, J
Published in: Infect Immun
October 15, 2021

Gamma interferon (IFN-γ)-induced immunity-related GTPases (IRGs) confer cell-autonomous immunity to the intracellular protozoan pathogen Toxoplasma gondii. Effector IRGs are loaded onto the Toxoplasma-containing parasitophorous vacuole (PV), where they recruit ubiquitin ligases, ubiquitin-binding proteins, and IFN-γ-inducible guanylate-binding proteins (Gbps), prompting PV lysis and parasite destruction. Host cells lacking the regulatory IRGs Irgm1 and Irgm3 fail to load effector IRGs, ubiquitin, and Gbps onto the PV and are consequently defective for cell-autonomous immunity to Toxoplasma. However, the role of the third regulatory IRG, Irgm2, in cell-autonomous immunity to Toxoplasma has remained unexplored. Here, we report that Irgm2 unexpectedly plays a limited role in the targeting of effector IRGs, ubiquitin, and Gbps to the Toxoplasma PV. Instead, Irgm2 is instrumental in the decoration of PVs with γ-aminobutyric acid receptor-associated protein-like 2 (GabarapL2). Cells lacking Irgm2 are as defective for cell-autonomous host defense to Toxoplasma as pan-Irgm-/- cells lacking all three Irgm proteins, and Irgm2-/- mice succumb to Toxoplasma infections as readily as pan-Irgm-/- mice. These findings demonstrate that, relative to Irgm1 and Irgm3, Irgm2 plays a distinct but critically important role in host resistance to Toxoplasma.

Duke Scholars

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

October 15, 2021

Volume

89

Issue

11

Start / End Page

e0020221

Location

United States

Related Subject Headings

  • Vacuoles
  • Ubiquitin
  • Toxoplasmosis
  • Microtubule-Associated Proteins
  • Microbiology
  • Mice, Inbred C57BL
  • Mice
  • GTP-Binding Proteins
  • GTP Phosphohydrolases
  • Apoptosis Regulatory Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dockterman, J., Fee, B. E., Taylor, G. A., & Coers, J. (2021). Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii. Infect Immun, 89(11), e0020221. https://doi.org/10.1128/IAI.00202-21
Dockterman, Jacob, Brian E. Fee, Gregory A. Taylor, and Jörn Coers. “Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii.Infect Immun 89, no. 11 (October 15, 2021): e0020221. https://doi.org/10.1128/IAI.00202-21.
Dockterman J, Fee BE, Taylor GA, Coers J. Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii. Infect Immun. 2021 Oct 15;89(11):e0020221.
Dockterman, Jacob, et al. “Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii.Infect Immun, vol. 89, no. 11, Oct. 2021, p. e0020221. Pubmed, doi:10.1128/IAI.00202-21.
Dockterman J, Fee BE, Taylor GA, Coers J. Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii. Infect Immun. 2021 Oct 15;89(11):e0020221.

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

October 15, 2021

Volume

89

Issue

11

Start / End Page

e0020221

Location

United States

Related Subject Headings

  • Vacuoles
  • Ubiquitin
  • Toxoplasmosis
  • Microtubule-Associated Proteins
  • Microbiology
  • Mice, Inbred C57BL
  • Mice
  • GTP-Binding Proteins
  • GTP Phosphohydrolases
  • Apoptosis Regulatory Proteins