Association between genetic variants in the IRGM gene and tuberculosis in a Korean population

Song, J. H.; Kim, S. Y.; Chung, Kyung Soo; Moon, Chang Mo; Kim, S. W.; Kim, E. Y.; Jung, Ji Ye; Park, Moo Suk; Kim, Y. S.; Chang, Joon; Shin, Dong Jik; Kang, Young Ae

doi:10.1007/s15010-014-0604-6

Cited by 16 publications

(16 citation statements)

References 18 publications

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“…In the same Ghanaian population, this allele was not associated with protection from TB caused by M. africanum or M. bovis . Several other studies variously identified associations of polymorphic IRGM alleles with protection or susceptibility to TB in African-American, Iranian, Chinese and Korean populations [191-194]. In some cases opposing effects on TB susceptibility were associated with the same allele in different populations.…”

Section: Autophagy In Tbmentioning

confidence: 99%

Cell death and autophagy in tuberculosis

Moraco

Kornfeld

2014

Seminars in Immunology

103

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Mycobacterium tuberculosis has succeeded in infecting one third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease.

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Section: Autophagy In Tbmentioning

confidence: 99%

Cell death and autophagy in tuberculosis

Moraco

Kornfeld

2014

Seminars in Immunology

103

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“…IRGM resists to the intracellular bacterium as a member of the GTPases family (Kim et al, ). Recent studies have shown that IRGM is mainly associated with chronic infectious diseases or inflammatory bowel diseases (Song et al, ; Iida et al, ). Importantly, IRGM can promote tumorigenesis and cell growth in melanoma and hepatocellular carcinoma (Dong et al, ; Wang et al, ).…”

Section: Introductionmentioning

confidence: 99%

IRGM promotes glioma M2 macrophage polarization through p62/TRAF6/NF‐κB pathway mediated IL‐8 production

Liao

Liu

et al. 2019

Cell Biology International

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Alternatively activated (M2) macrophage promotes glioma progression and immune escape as the most immunocyte in glioma microenvironment. Finding out the key protein regulating M2 macrophage polarization is necessary for improving treatment. Whether immunity related GTPase M (IRGM) is involved in glioma development and M2 macrophage polarization is unknown. IRGM and M2 macrophage marker CD206 expression were examined using immunohistochemistry among 35 glioma and 11 non-cancerous brain specimens. We found IRGM scores were positively correlated with CD206 scores in glioma specimens and monocyte proportion in blood samples. A172 glioma cells transfected with either IRGM knock-down lentivirus (Lenti-IRGM) or control lentivirus (Lenti-HK) were subcutaneously injected into nude mice. In vivo, xenografted glioma size of the Lenti-IRGM group was smaller and had weaker fluorescence signal than Lenti-HK control group. Immunofluorescence results showed that there was obviously decreased IRGM, CD206, and IL-8 expression in the mice glioma of Lenti-IRGM group than Lenti-HK control group. In vitro, flow cytometry results showed that M2 polarization from THP-1 cocultured with Lenti-IRGM glioma cells decreased in contrast to that with Lenti-HK glioma cells; there were less interleukin-8 (IL-8) and macrophage inflammation protein 3-a (MIP-3a), but more interleukin-6 (IL-6) in the supernatant of Lenti-IRGM glioma cells than matched control. Western blot and immunofluorescence displayed that IRGM strongly promoted sequestosome-1 (p62/SQSTM1), necrosis factor receptoractivating factor 6 (TRAF6) expression and NF-kB transportation to the nucleus. Realtime PCR results demonstrated IRGM also promoted NF-kB downstream cytokines IL-8 and MIP-3a mRNA expression. These data suggested that IRGM could promote glioma development and M2 macrophage polarization by regulating p62/TRAF6/NF-kB pathway-mediated IL-8 production.

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“…The human population polymorphisms in IRGM have been linked to autophagy (Consortium, 2007; Craddock et al, 2010) and to its effector outputs including direct antimicrobial defense (Brest et al, 2011; McCarroll et al, 2008). In keeping with its autophagy-mediated antimicrobial role, IRGM is additionally a genetic risk factor for tuberculosis in different human populations (Intemann et al, 2009; Song et al, 2014) and may afford protection in leprosy (Yang et al, 2014). However, the molecular mechanism of IRGM’s function in autophagy has remained a mystery.…”

Section: Introductionmentioning

confidence: 99%

IRGM Governs the Core Autophagy Machinery to Conduct Antimicrobial Defense

2015

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SUMMARY IRGM, encoded by a uniquely human gene conferring risk for inflammatory diseases, affects autophagy through a hitherto unknown mechanism. Here we show how IRGM controls autophagy. IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly thus governing the formation of autophagy initiation complexes. We further show that IRGM interacts with pattern recognition receptors including NOD2. IRGM, NOD2 and ATG16L1, all of which are Crohn’s disease risk factors, form a molecular complex to modulate autophagic responses to microbial products. NOD2 enhances K63-linked polyubiquitination of IRGM, which is required for interactions of IRGM with the core autophagy factors and for microbial clearance. Thus, IRGM plays a direct role in organizing the core autophagy machinery to endow it with antimicrobial and anti-inflammatory functions.

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Association between genetic variants in the IRGM gene and tuberculosis in a Korean population

Cited by 16 publications

References 18 publications

Cell death and autophagy in tuberculosis

Cell death and autophagy in tuberculosis

IRGM promotes glioma M2 macrophage polarization through p62/TRAF6/NF‐κB pathway mediated IL‐8 production

IRGM Governs the Core Autophagy Machinery to Conduct Antimicrobial Defense

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