Polymorphisms in Autophagy Genes and Susceptibility to Tuberculosis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Aug 11

PMID 22879892

Citations 33

Authors

Mario Songane

Johanneke Kleinnijenhuis

Bachti Alisjahbana

Edhyana Sahiratmadja

Ida Parwati

Marije Oosting

Theo S Plantinga

Leo A B Joosten

Mihai G Netea

Tom H M Ottenhoff

Esther van de Vosse

Reinout van Crevel

Affiliations

Soon will be listed here.

Abstract

Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.

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References

Kleinnijenhuis J, Oosting M, Plantinga T, van der Meer J, Joosten L, Crevel R . Autophagy modulates the Mycobacterium tuberculosis-induced cytokine response. Immunology. 2011; 134(3):341-8. PMC: 3209573. DOI: 10.1111/j.1365-2567.2011.03494.x. View

Kumar D, Nath L, Kamal M, Varshney A, Jain A, Singh S . Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell. 2010; 140(5):731-43. DOI: 10.1016/j.cell.2010.02.012. View

Epstein J, Victor T, Hon D, Lewis L, Beyers N, Zurakowski D . Mannose-binding protein B allele confers protection against tuberculous meningitis. Pediatr Res. 1999; 45(4 Pt 1):459-64. DOI: 10.1203/00006450-199904010-00002. View

Eskelinen E . Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med. 2006; 27(5-6):495-502. DOI: 10.1016/j.mam.2006.08.005. View

Bornman L, Campbell S, Fielding K, Bah B, Sillah J, Gustafson P . Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study. J Infect Dis. 2004; 190(9):1631-41. DOI: 10.1086/424462. View

Davila S, Hibberd M, Dass R, Wong H, Sahiratmadja E, Bonnard C . Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis. PLoS Genet. 2008; 4(10):e1000218. PMC: 2568981. DOI: 10.1371/journal.pgen.1000218. View

Gagneux S, Small P . Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. Lancet Infect Dis. 2007; 7(5):328-37. DOI: 10.1016/S1473-3099(07)70108-1. View

Gutierrez M, Master S, Singh S, Taylor G, Colombo M, Deretic V . Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004; 119(6):753-66. DOI: 10.1016/j.cell.2004.11.038. View

Intemann C, Thye T, Niemann S, Browne E, Chinbuah M, Enimil A . Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS Pathog. 2009; 5(9):e1000577. PMC: 2735778. DOI: 10.1371/journal.ppat.1000577. View

10.

Plantinga T, Crisan T, Oosting M, van de Veerdonk F, de Jong D, Philpott D . Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2. Gut. 2011; 60(9):1229-35. DOI: 10.1136/gut.2010.228908. View

11.

Goren M, DARCY HART P, Young M, Armstrong J . Prevention of phagosome-lysosome fusion in cultured macrophages by sulfatides of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1976; 73(7):2510-4. PMC: 430628. DOI: 10.1073/pnas.73.7.2510. View

12.

Xie Z, Klionsky D . Autophagosome formation: core machinery and adaptations. Nat Cell Biol. 2007; 9(10):1102-9. DOI: 10.1038/ncb1007-1102. View

13.

Sehgal R, Berg A, Polinski J, Hegarty J, Lin Z, McKenna K . Mutations in IRGM are associated with more frequent need for surgery in patients with ileocolonic Crohn's disease. Dis Colon Rectum. 2012; 55(2):115-21. DOI: 10.1097/DCR.0b013e31823ccea8. View

14.

van Crevel R, Nelwan R, de Lenne W, Veeraragu Y, van der Zanden A, Amin Z . Mycobacterium tuberculosis Beijing genotype strains associated with febrile response to treatment. Emerg Infect Dis. 2001; 7(5):880-3. PMC: 2631862. DOI: 10.3201/eid0705.017518. View

15.

Yuk J, Shin D, Lee H, Yang C, Jin H, Kim K . Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009; 6(3):231-43. DOI: 10.1016/j.chom.2009.08.004. View

16.

Cheng J, Ning Y, Zhang W, Lu Z, Lin L . T300A polymorphism of ATG16L1 and susceptibility to inflammatory bowel diseases: a meta-analysis. World J Gastroenterol. 2010; 16(10):1258-66. PMC: 2839180. DOI: 10.3748/wjg.v16.i10.1258. View

17.

Deretic V, Levine B . Autophagy, immunity, and microbial adaptations. Cell Host Microbe. 2009; 5(6):527-49. PMC: 2720763. DOI: 10.1016/j.chom.2009.05.016. View

18.

Vergne I, Chua J, Singh S, Deretic V . Cell biology of mycobacterium tuberculosis phagosome. Annu Rev Cell Dev Biol. 2004; 20:367-94. DOI: 10.1146/annurev.cellbio.20.010403.114015. View

19.

Biswas D, Qureshi O, Lee W, Croudace J, Mura M, Lammas D . ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages. BMC Immunol. 2008; 9:35. PMC: 2483257. DOI: 10.1186/1471-2172-9-35. View

20.

MacMicking J, Taylor G, McKinney J . Immune control of tuberculosis by IFN-gamma-inducible LRG-47. Science. 2003; 302(5645):654-9. DOI: 10.1126/science.1088063. View