Immuno-metabolic profile of human macrophages after Leishmania and Trypanosoma cruzi infection


Autoři: Maureen C. Ty aff001;  P’ng Loke aff001;  Jordi Alberola aff002;  Ana Rodriguez aff001;  Alheli Rodriguez-Cortes aff001
Působiště autorů: New York University School of Medicine, Department of Microbiology, New York, NY, United States of America aff001;  Dept Farmacologia, Toxicologia i Terapeutica, Facultat de Veterinaria, Edifici V, Universitat Autonoma de Barcelona, Bellaterra, Spain aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225588

Souhrn

Macrophages can reprogram their metabolism in response to the surrounding stimuli, which affects their capacity to kill intracellular pathogens. We have investigated the metabolic and immune status of human macrophages after infection with the intracellular trypanosomatid parasites Leishmania donovani, L. amazonensis and T. cruzi and their capacity to respond to a classical polarizing stimulus (LPS and IFN-γ). We found that macrophages infected with Leishmania preferentially upregulate oxidative phosphorylation, which could be contributed by both host cell and parasite, while T. cruzi infection did not significantly increase glycolysis or oxidative phosphorylation. Leishmania and T. cruzi infect macrophages without triggering a strong inflammatory cytokine response, but infection does not prevent a potent response to LPS and IFN-γ. Infection appears to prime macrophages, since the cytokine response to activation with LPS and IFN-γ is more intense in infected macrophages compared to uninfected ones. Metabolic polarization in macrophages can influence infection and immune evasion of these parasites since preventing macrophage cytokine responses would help parasites to establish a persistent infection. However, macrophages remain responsive to classical inflammatory stimuli and could still trigger inflammatory cytokine secretion by macrophages.

Klíčová slova:

Cytokines – Glycolysis – Inflammation – Macrophages – Parasitic diseases – Respiratory infections – Trypanosoma cruzi – Leishmania donovani


Zdroje

1. Saha S, Shalova IN, Biswas SK. Metabolic regulation of macrophage phenotype and function. Immunol Rev. 2017;280(1):102–11. Epub 2017/10/14. doi: 10.1111/imr.12603 29027220.

2. Jha AK, Huang SC, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015;42(3):419–30. doi: 10.1016/j.immuni.2015.02.005 25786174.

3. Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013;38(4):633–43. doi: 10.1016/j.immuni.2013.04.005 23601682; PubMed Central PMCID: PMC3654249.

4. Haschemi A, Kosma P, Gille L, Evans CR, Burant CF, Starkl P, et al. The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 2012;15(6):813–26. doi: 10.1016/j.cmet.2012.04.023 22682222; PubMed Central PMCID: PMC3370649.

5. O'Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213(1):15–23. Epub 2015/12/24. doi: 10.1084/jem.20151570 26694970; PubMed Central PMCID: PMC4710204.

6. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, et al. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature. 2013;496(7444):238–42. doi: 10.1038/nature11986 23535595; PubMed Central PMCID: PMC4031686.

7. Palsson-McDermott EM, Curtis AM, Goel G, Lauterbach MA, Sheedy FJ, Gleeson LE, et al. Pyruvate kinase M2 regulates Hif-1alpha activity and IL-1beta induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015;21(1):65–80. doi: 10.1016/j.cmet.2014.12.005 25565206; PubMed Central PMCID: PMC5198835.

8. Millet P, Vachharajani V, McPhail L, Yoza B, McCall CE. GAPDH Binding to TNF-alpha mRNA Contributes to Posttranscriptional Repression in Monocytes: A Novel Mechanism of Communication between Inflammation and Metabolism. J Immunol. 2016;196(6):2541–51. doi: 10.4049/jimmunol.1501345 26843329; PubMed Central PMCID: PMC4779706.

9. Infantino V, Convertini P, Cucci L, Panaro MA, Di Noia MA, Calvello R, et al. The mitochondrial citrate carrier: a new player in inflammation. Biochem J. 2011;438(3):433–6. doi: 10.1042/BJ20111275 21787310.

10. Huang SC, Smith AM, Everts B, Colonna M, Pearce EL, Schilling JD, et al. Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation. Immunity. 2016;45(4):817–30. Epub 2016/10/21. doi: 10.1016/j.immuni.2016.09.016 27760338; PubMed Central PMCID: PMC5535820.

11. Tan Z, Xie N, Cui H, Moellering DR, Abraham E, Thannickal VJ, et al. Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via regulating glucose metabolism. J Immunol. 2015;194(12):6082–9. doi: 10.4049/jimmunol.1402469 25964487; PubMed Central PMCID: PMC4458459.

12. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab. 2006;4(1):13–24. doi: 10.1016/j.cmet.2006.05.011 16814729; PubMed Central PMCID: PMC1904486.

13. Geeraerts X, Bolli E, Fendt SM, Van Ginderachter JA. Macrophage Metabolism As Therapeutic Target for Cancer, Atherosclerosis, and Obesity. Front Immunol. 2017;8:289. doi: 10.3389/fimmu.2017.00289 28360914; PubMed Central PMCID: PMC5350105.

14. Rossi M, Fasel N. How to master the host immune system? Leishmania parasites have the solutions! Int Immunol. 2017. Epub 2018/01/03. doi: 10.1093/intimm/dxx075 29294040.

15. Fernandes MC, Andrews NW. Host cell invasion by Trypanosoma cruzi: a unique strategy that promotes persistence. FEMS Microbiol Rev. 2012;36(3):734–47. Epub 2012/02/22. doi: 10.1111/j.1574-6976.2012.00333.x 22339763; PubMed Central PMCID: PMC3319478.

16. Andriani G, Chessler AD, Courtemanche G, Burleigh BA, Rodriguez A. Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. PLoS Negl Trop Dis. 2011;5(8):e1298. doi: 10.1371/journal.pntd.0001298 21912715; PubMed Central PMCID: PMC3166044.

17. Buckner FS, Wilson AJ. Colorimetric assay for screening compounds against Leishmania amastigotes grown in macrophages. Am J Trop Med Hyg. 2005;72(5):600–5. Epub 2005/05/14. 15891135.

18. Martinez FO, Gordon S. The evolution of our understanding of macrophages and translation of findings toward the clinic. Expert Rev Clin Immunol. 2015;11(1):5–13. doi: 10.1586/1744666X.2015.985658 25434688.

19. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20. Epub 2014/07/19. doi: 10.1016/j.immuni.2014.06.008 25035950; PubMed Central PMCID: PMC4123412.

20. Gleeson LE, Sheedy FJ, Palsson-McDermott EM, Triglia D, O'Leary SM, O'Sullivan MP, et al. Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication. J Immunol. 2016;196(6):2444–9. Epub 2016/02/14. doi: 10.4049/jimmunol.1501612 26873991.

21. Czyz DM, Willett JW, Crosson S. Brucella abortus Induces a Warburg Shift in Host Metabolism That Is Linked to Enhanced Intracellular Survival of the Pathogen. J Bacteriol. 2017;199(15). Epub 2017/06/01. doi: 10.1128/JB.00227-17 28559292; PubMed Central PMCID: PMC5512224.

22. Tomiotto-Pellissier F, Bortoleti B, Assolini JP, Goncalves MD, Carloto ACM, Miranda-Sapla MM, et al. Macrophage Polarization in Leishmaniasis: Broadening Horizons. Front Immunol. 2018;9:2529. doi: 10.3389/fimmu.2018.02529 30429856; PubMed Central PMCID: PMC6220043.

23. Zanluqui NG, Wowk PF, Pinge-Filho P. Machrophage Polarization in Chagas Disease. Journal of Clinical & Cellular Immunology. 2015;6(2).

24. Koo SJ, Chowdhury IH, Szczesny B, Wan X, Garg NJ. Macrophages Promote Oxidative Metabolism To Drive Nitric Oxide Generation in Response to Trypanosoma cruzi. Infect Immun. 2016;84(12):3527–41. Epub 2016/10/05. doi: 10.1128/IAI.00809-16 27698021; PubMed Central PMCID: PMC5116729.

25. Zhang S, Kim CC, Batra S, McKerrow JH, Loke P. Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. PLoS Negl Trop Dis. 2010;4(3):e648. Epub 2010/04/03. doi: 10.1371/journal.pntd.0000648 20361029; PubMed Central PMCID: PMC2846935.

26. Dey N, Sinha M, Gupta S, Gonzalez MN, Fang R, Endsley JJ, et al. Caspase-1/ASC inflammasome-mediated activation of IL-1beta-ROS-NF-kappaB pathway for control of Trypanosoma cruzi replication and survival is dispensable in NLRP3-/- macrophages. PLoS One. 2014;9(11):e111539. Epub 2014/11/06. doi: 10.1371/journal.pone.0111539 25372293; PubMed Central PMCID: PMC4221042.

27. Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol. 2015;7(5). Epub 2015/01/31. doi: 10.1101/cshperspect.a016303 25635046; PubMed Central PMCID: PMC4448619.

28. Hardison JL, Wrightsman RA, Carpenter PM, Lane TE, Manning JE. The chemokines CXCL9 and CXCL10 promote a protective immune response but do not contribute to cardiac inflammation following infection with Trypanosoma cruzi. Infect Immun. 2006;74(1):125–34. Epub 2005/12/22. doi: 10.1128/IAI.74.1.125-134.2006 16368965; PubMed Central PMCID: PMC1346648.

29. Caradonna KL, Engel JC, Jacobi D, Lee CH, Burleigh BA. Host metabolism regulates intracellular growth of Trypanosoma cruzi. Cell Host Microbe. 2013;13(1):108–17. Epub 2013/01/22. doi: 10.1016/j.chom.2012.11.011 23332160; PubMed Central PMCID: PMC3560928.

30. Shah-Simpson S, Lentini G, Dumoulin PC, Burleigh BA. Modulation of host central carbon metabolism and in situ glucose uptake by intracellular Trypanosoma cruzi amastigotes. PLoS Pathog. 2017;13(11):e1006747. Epub 2017/11/28. doi: 10.1371/journal.ppat.1006747 29176805; PubMed Central PMCID: PMC5720825.

31. Mehta MM, Weinberg SE, Chandel NS. Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol. 2017;17(10):608–20. doi: 10.1038/nri.2017.66 28669986.

32. Moreira D, Rodrigues V, Abengozar M, Rivas L, Rial E, Laforge M, et al. Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. PLoS Pathog. 2015;11(3):e1004684. doi: 10.1371/journal.ppat.1004684 25738568; PubMed Central PMCID: PMC4349736.

33. Osorio EY, Travi BL, da Cruz AM, Saldarriaga OA, Medina AA, Melby PC. Growth factor and Th2 cytokine signaling pathways converge at STAT6 to promote arginase expression in progressive experimental visceral leishmaniasis. PLoS Pathog. 2014;10(6):e1004165. doi: 10.1371/journal.ppat.1004165 24967908; PubMed Central PMCID: PMC4072777.

34. Belkaid Y, Mendez S, Lira R, Kadambi N, Milon G, Sacks D. A natural model of Leishmania major infection reveals a prolonged "silent" phase of parasite amplification in the skin before the onset of lesion formation and immunity. J Immunol. 2000;165(2):969–77. doi: 10.4049/jimmunol.165.2.969 10878373.

35. Fernandes MC, Dillon LA, Belew AT, Bravo HC, Mosser DM, El-Sayed NM. Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures. MBio. 2016;7(3). doi: 10.1128/mBio.00027-16 27165796; PubMed Central PMCID: PMC4959658.

36. Kim J, Kwak HJ, Cha JY, Jeong YS, Rhee SD, Kim KR, et al. Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction. J Biol Chem. 2014;289(33):23246–55. doi: 10.1074/jbc.M114.577908 24973221; PubMed Central PMCID: PMC4132821.

37. Van den Bossche J, Baardman J, Otto NA, van der Velden S, Neele AE, van den Berg SM, et al. Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages. Cell Rep. 2016;17(3):684–96. doi: 10.1016/j.celrep.2016.09.008 27732846.


Článek vyšel v časopise

PLOS One


2019 Číslo 12