دورية أكاديمية
أعرض في EDS

Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis.

التفاصيل البيبلوغرافية
العنوان: Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis.
المؤلفون: Rahman MA; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa., Cumming BM; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa., Addicott KW; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa., Pacl HT; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294., Russell SL; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa., Nargan K; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa., Naidoo T; Department of Anatomical Pathology, National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, 4091 Durban, South Africa., Ramdial PK; Department of Anatomical Pathology, National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, 4091 Durban, South Africa., Adamson JH; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa., Wang R; Department of Biology, York University, Toronto, ON M3J 1P3, Canada., Steyn AJC; Africa Health Research Institute, 4001 Durban, KwaZulu Natal, South Africa; asteyn@uab.edu.; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294.; Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Mar 24; Vol. 117 (12), pp. 6663-6674. Date of Electronic Publication: 2020 Mar 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Carbon/*metabolism , Cystathionine gamma-Lyase/*physiology , Hydrogen Sulfide/*toxicity , Mycobacterium tuberculosis/*immunology , Tuberculosis, Pulmonary/*etiology, Alkynes/pharmacology ; Animals ; Cystathionine gamma-Lyase/antagonists & inhibitors ; Cytokines/metabolism ; Enzyme Inhibitors/pharmacology ; Glycine/analogs & derivatives ; Glycine/pharmacology ; Glycolysis ; Hydrogen Sulfide/metabolism ; Lymphocytes/drug effects ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mycobacterium tuberculosis/drug effects ; Myeloid Cells/drug effects ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Signal Transduction ; Tuberculosis, Pulmonary/metabolism ; Tuberculosis, Pulmonary/pathology
مستخلص: The ubiquitous gasotransmitter hydrogen sulfide (H 2 S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H 2 S in Mycobacterium tuberculosis ( Mtb ) pathogenesis. We showed that Mtb- infected CSE -/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE -/- cells. Chemical complementation of infected WT and CSE -/- macrophages using the slow H 2 S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H 2 S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1β, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE -/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H 2 S and central metabolism. Our data suggest that excessive H 2 S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H 2 S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
Competing Interests: The authors declare no competing interest.
(Copyright © 2020 the Author(s). Published by PNAS.)
References: FASEB J. 2005 Apr;19(6):623-5. (PMID: 15671155)
Microbiol Spectr. 2016 Oct;4(5):. (PMID: 27763255)
Trends Biochem Sci. 2014 May;39(5):227-32. (PMID: 24767680)
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20477-82. (PMID: 21059928)
J Exp Med. 2018 Apr 2;215(4):1135-1152. (PMID: 29500179)
Biochem Biophys Res Commun. 2009 Feb 27;380(1):153-9. (PMID: 19166813)
Trends Biochem Sci. 2015 Nov;40(11):687-700. (PMID: 26439534)
Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1193-201. (PMID: 16428267)
Infect Immun. 2011 May;79(5):1842-7. (PMID: 21321074)
PLoS One. 2016 Aug 12;11(8):e0160521. (PMID: 27518439)
Annu Rev Immunol. 1997;15:323-50. (PMID: 9143691)
J Biol Chem. 2008 Jun 27;283(26):18032-9. (PMID: 18400743)
Br J Pharmacol. 2012 Dec;167(7):1492-505. (PMID: 22831549)
Cell Metab. 2017 Jun 6;25(6):1254-1268.e7. (PMID: 28591633)
Blood. 2012 Aug 16;120(7):1422-31. (PMID: 22786879)
Can J Biochem. 1982 Jun;60(6):613-23. (PMID: 6288202)
Nature. 2013 Apr 11;496(7444):238-42. (PMID: 23535595)
Nitric Oxide. 2016 Sep 30;59:28-41. (PMID: 27387335)
Cell Biol Int. 2010 Mar 29;34(5):477-84. (PMID: 20067446)
Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16633-8. (PMID: 19805349)
Biochem Soc Trans. 2013 Oct;41(5):1312-6. (PMID: 24059525)
Cell Rep. 2018 Nov 13;25(7):1938-1952.e5. (PMID: 30428359)
J Biol Chem. 2012 Feb 3;287(6):4211-21. (PMID: 22167178)
Immunity. 2013 Apr 18;38(4):633-43. (PMID: 23601682)
Br J Pharmacol. 2014 Apr;171(8):2099-122. (PMID: 23991830)
J Cell Sci. 2006 Jun 1;119(Pt 11):2291-8. (PMID: 16723735)
Semin Immunol. 2016 Oct;28(5):450-468. (PMID: 27780657)
J Immunol. 2013 Apr 15;190(8):4196-204. (PMID: 23487424)
Mol Med. 2010 Sep-Oct;16(9-10):417-24. (PMID: 20440442)
J Biol Chem. 2018 Feb 16;293(7):2546-2557. (PMID: 29279328)
J Exp Med. 2011 Oct 24;208(11):2251-62. (PMID: 21967766)
Sci Total Environ. 2019 May 1;663:380-386. (PMID: 30716628)
Antioxid Redox Signal. 2012 Feb 1;16(3):203-16. (PMID: 22004513)
Nat Rev Drug Discov. 2015 May;14(5):329-45. (PMID: 25849904)
Antioxid Redox Signal. 2010 May 15;12(10):1147-54. (PMID: 19769459)
Exp Ther Med. 2015 Mar;9(3):1068-1074. (PMID: 25667680)
J Clin Invest. 2016 Oct 3;126(10):3699-3707. (PMID: 27571407)
Cell Rep. 2019 Dec 10;29(11):3564-3579.e5. (PMID: 31825836)
Cancer Res. 2012 Aug 1;72(15):3709-14. (PMID: 22787121)
Trends Immunol. 2017 Jun;38(6):395-406. (PMID: 28396078)
Elife. 2018 Nov 16;7:. (PMID: 30444490)
J Immunol. 2016 Aug 15;197(4):1287-97. (PMID: 27430718)
Expert Rev Clin Pharmacol. 2011 Jan;4(1):13-32. (PMID: 22115346)
Nat Rev Immunol. 2016 Sep;16(9):553-65. (PMID: 27396447)
Mediators Inflamm. 2017;2017:9029327. (PMID: 29386753)
Br J Pharmacol. 2016 May;173(9):1556-65. (PMID: 26890936)
J Exp Med. 2003 Sep 1;198(5):705-13. (PMID: 12953092)
Front Immunol. 2018 May 03;9:860. (PMID: 29774023)
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2943-8. (PMID: 22323590)
FASEB J. 2002 Nov;16(13):1792-8. (PMID: 12409322)
Front Immunol. 2018 Feb 05;9:141. (PMID: 29459863)
Science. 2008 Oct 24;322(5901):587-90. (PMID: 18948540)
Cell. 2016 Oct 6;167(2):457-470.e13. (PMID: 27667687)
Front Immunol. 2017 Jun 30;8:772. (PMID: 28713389)
Br J Pharmacol. 2014 Apr;171(8):2123-46. (PMID: 23991749)
Front Immunol. 2016 Apr 21;7:145. (PMID: 27148264)
J Immunol. 2011 Nov 1;187(9):4778-87. (PMID: 21957141)
معلومات مُعتمدة: R01 AI111940 United States AI NIAID NIH HHS; R01 AI134810 United States AI NIAID NIH HHS; R01 AI137043 United States AI NIAID NIH HHS; R21 AI127182 United States AI NIAID NIH HHS; R61 AI138280 United States AI NIAID NIH HHS; P30 DK079626 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: H2S; hydrogen sulfide; metabolism; pathogenesis; tuberculosis
المشرفين على المادة: 0 (Alkynes)
0 (Cytokines)
0 (Enzyme Inhibitors)
64165-64-6 (propargylglycine)
7440-44-0 (Carbon)
EC 4.4.1.1 (Cystathionine gamma-Lyase)
TE7660XO1C (Glycine)
YY9FVM7NSN (Hydrogen Sulfide)
تواريخ الأحداث: Date Created: 20200307 Date Completed: 20200707 Latest Revision: 20200707
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7104411
DOI: 10.1073/pnas.1919211117
PMID: 32139610
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1919211117