ArticlePLoS pathogens2009
Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 3 of them syntheses that pooled it.
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Who cites it
130 citing papers in PubMed, 3 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Macrophage migration inhibitory factor-794 CATT microsatellite polymorphism and risk of tuberculosis: a meta-analysis.Bioscience reports · 2018Pooled it
- Pooled it
- Common variants at 11p13 are associated with susceptibility to tuberculosis.Nature genetics · 2012Pooled it
- Human Genetic Variation Associates With Infection by Derived Ugandan M. tuberculosis Lineage.The Journal of infectious diseases · 2026Article
- Irgm1 Restrains CD8European journal of immunology · 2026Article
- Functional single nucleotide polymorphisms in CACNA2D3 and other autophagy-related genes are associated with leprosy among Brazilians.PLoS neglected tropical diseases · 2026Article
- Differential roles for Irgm1 in myeloid cells for immune resistance to pathogenic bacteria.Journal of leukocyte biology · 2025Article
- Using host and bacterial genetic approaches to define virulence strategies and protective immunity duringmSphere · 2025Review
- Autophagy in mycobacterial infections: molecular mechanisms, host-pathogen interactions, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2025Review
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
- Type I interferon signaling and peroxisomal dysfunction contribute to enhanced inflammatory cytokine production in IRGM1-deficient macrophages.The Journal of biological chemistry · 2024Article
- Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania.Scientific reports · 2024Article
- Article
- Differential Requirement for IRGM Proteins during Tuberculosis Infection in Mice.Infection and immunity · 2023Article
- Review
- Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.The EMBO journal · 2022Article
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- How did we get here? Insights into mechanisms of immunity-related GTPase targeting to intracellular pathogens.Current opinion in microbiology · 2022Review
- Immunity-related GTPase IRGM at the intersection of autophagy, inflammation, and tumorigenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- A guide to membrane atg8ylation and autophagy with reflections on immunity.The Journal of cell biology · 2022Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype -261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52-0.84, P(nominal) 0.0009, P(corrected) 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70-1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49-0.81, P(nominal) 0.0004, P(corrected) 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants -261C and -261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM -261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population.
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