Mycobacterial Trehalose 6,6'-Dimycolate-Induced M1-Type Inflammation

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2019 Nov 18

PMID 31734231

Citations 8

Authors

Thao K T Nguyen

John dAigle

Luis Chinea

Zainab Niaz

Robert L Hunter

Shen-An Hwang

Jeffrey K Actor

Affiliations

Soon will be listed here.

Abstract

Murine models of Mycobacterium tuberculosis (Mtb) infection demonstrate progression of M1-like (proinflammatory) and M2-like (anti-inflammatory) macrophage morphology following primary granuloma formation. The Mtb cell wall cording factor, trehalose 6,6'-dimycolate (TDM), is a physiologically relevant and useful molecule for modeling early macrophage-mediated events during establishment of the tuberculosis-induced granuloma pathogenesis. Here, it is shown that TDM is a major driver of the early M1-like macrophage response as seen during initiation of the granulomas of primary pathology. Proinflammatory cytokines tumor necrosis factor-α, IL-1β, IL-6, and IL-12p40 are produced in lung tissue after administration of TDM to mice. Furthermore, CD11bCD45 macrophages with a high surface expression of the M1-like markers CD38 and CD86 were found present in regions of pathology in lungs of mice at 7 days post-TDM introduction. Conversely, only low phenotypic marker expression of M2-like markers CD206 and EGR-2 were present on macrophages. These findings suggest that TDM plays a role in establishment of the M1-like shift in the microenvironment during primary tuberculosis.

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References

Guidry T, Olsen M, Kil K, Hunter Jr R, Geng Y, Actor J . Failure of CD1D-/- mice to elicit hypersensitive granulomas to mycobacterial cord factor trehalose 6,6'-dimycolate. J Interferon Cytokine Res. 2004; 24(6):362-71. DOI: 10.1089/107999004323142222. View

Davis M, Tsang T, Qiu Y, Dayrit J, Freij J, Huffnagle G . Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection. mBio. 2013; 4(3):e00264-13. PMC: 3684832. DOI: 10.1128/mBio.00264-13. View

Pelletier M, Forget A, Bourassa D, Gros P, Skamene E . Immunopathology of BCG infection in genetically resistant and susceptible mouse strains. J Immunol. 1982; 129(5):2179-85. View

Orme I, Robinson R, Cooper A . The balance between protective and pathogenic immune responses in the TB-infected lung. Nat Immunol. 2014; 16(1):57-63. DOI: 10.1038/ni.3048. View

Perez R, Roman J, Staton Jr G, Hunter R . Extravascular coagulation and fibrinolysis in murine lung inflammation induced by the mycobacterial cord factor trehalose-6,6'-dimycolate. Am J Respir Crit Care Med. 1994; 149(2 Pt 1):510-8. DOI: 10.1164/ajrccm.149.2.8306054. View

Yue Y, Huang W, Liang J, Guo J, Ji J, Yao Y . IL4I1 Is a Novel Regulator of M2 Macrophage Polarization That Can Inhibit T Cell Activation via L-Tryptophan and Arginine Depletion and IL-10 Production. PLoS One. 2015; 10(11):e0142979. PMC: 4658051. DOI: 10.1371/journal.pone.0142979. View

Dorhoi A, Reece S, Kaufmann S . For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection. Immunol Rev. 2011; 240(1):235-51. DOI: 10.1111/j.1600-065X.2010.00994.x. View

Goldberg M, Saini N, Porcelli S . Evasion of Innate and Adaptive Immunity by Mycobacterium tuberculosis. Microbiol Spectr. 2015; 2(5). DOI: 10.1128/microbiolspec.MGM2-0005-2013. View

Rajaram M, Ni B, Dodd C, Schlesinger L . Macrophage immunoregulatory pathways in tuberculosis. Semin Immunol. 2014; 26(6):471-85. PMC: 4314327. DOI: 10.1016/j.smim.2014.09.010. View

10.

Schoenen H, Huber A, Sonda N, Zimmermann S, Jantsch J, Lepenies B . Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C/EBPβ and HIF1α. J Immunol. 2014; 193(7):3664-75. DOI: 10.4049/jimmunol.1301593. View

11.

Zhao X, Zhu L, Chang Q, Jiang C, You Y, Luo T . C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation. J Biol Chem. 2014; 289(43):30052-62. PMC: 4208012. DOI: 10.1074/jbc.M114.588574. View

12.

Kodar K, Harper J, McConnell M, Timmer M, Stocker B . The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling. Immun Inflamm Dis. 2017; 5(4):503-514. PMC: 5691301. DOI: 10.1002/iid3.186. View

13.

Sheng J, Ruedl C, Karjalainen K . Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells. Immunity. 2015; 43(2):382-93. DOI: 10.1016/j.immuni.2015.07.016. View

14.

Hao W, Schlesinger L, Friedman A . Modeling Granulomas in Response to Infection in the Lung. PLoS One. 2016; 11(3):e0148738. PMC: 4795641. DOI: 10.1371/journal.pone.0148738. View

15.

Viegas M, do Carmo A, Silva T, Seco F, Serra V, Lacerda M . CD38 plays a role in effective containment of mycobacteria within granulomata and polarization of Th1 immune responses against Mycobacterium avium. Microbes Infect. 2007; 9(7):847-54. DOI: 10.1016/j.micinf.2007.03.003. View

16.

Bloch H, NOLL H . Studies on the virulence of Tubercle bacilli; the effect of cord factor on murine tuberculosis. Br J Exp Pathol. 1955; 36(1):8-17. PMC: 2082506. View

17.

Dorhoi A, Kaufmann S . Versatile myeloid cell subsets contribute to tuberculosis-associated inflammation. Eur J Immunol. 2015; 45(8):2191-202. DOI: 10.1002/eji.201545493. View

18.

Behling C, Perez R, Kidd M, Staton Jr G, Hunter R . Induction of pulmonary granulomas, macrophage procoagulant activity, and tumor necrosis factor-alpha by trehalose glycolipids. Ann Clin Lab Sci. 1993; 23(4):256-66. View

19.

Kager L, Blok D, Lede I, Rahman W, Afroz R, Bresser P . Pulmonary tuberculosis induces a systemic hypercoagulable state. J Infect. 2014; 70(4):324-34. DOI: 10.1016/j.jinf.2014.10.006. View

20.

Syed S, Hunter Jr R . Studies on the toxic effects of quartz and a mycobacterial glycolipid, trehalose 6,6'-dimycolate. Ann Clin Lab Sci. 1997; 27(5):375-83. View