Comparison of pro-inflammatory cytokines (IL-6, IL-1α and IL-1β) released by MPI and MARCO (-/-) knockout cells when stimulated by heat killed fungi- Candida albicans and Aspergillus niger

Sherin Chacko

Abstract


Background: Alveolar Macrophages serve the first line of defence against invading pathogens within the lungs. During the innate immune response, they recognise pathogens such as Candida albicans and Aspergillus niger as “non-self”, phagocytosing them before the pathogen can infiltrate the body and cause disease. There are many Pattern Recognition Receptors (PRRs) that detect specific patterns on the pathogen (PAMPs), inducing an immune response which recruits different immune cells to the site of infection, releasing many cytokines that help with recruiting and clearance of the pathogen.  MARCO is a Scavenger receptor that has an important role in the recognition and response mechanisms and this experiment was carried out to confirm the role of MARCO receptors on MPI cells stimulated with heat killed fungi.

Method:  MPI cells were cultured, exposed to different concentrations of C.albicans, A.niger and Beta-glucan over a period of 16-18 hours and then quantified using ELISA. The cytokines measured were IL-6, IL-1α and IL-1β. The same procedures were carried out on MARCO-/- MPI cells too.

Results: The results show a significant difference in the amount of pro-inflammatory cytokines produced compared to the control, demonstrating that the immune response was instigated.

MARCO-/- cells showed no immune response compared to the control. They were also compared to the normally stimulated MPI cells.

Conclusion: The study consolidates the importance of the MARCO receptor in response to pathogens. 


Full Text:

PDF

References


Means TK. Fungal pathogen recognition by scavenger receptors in nematodes and mammals. Virulence. 2010;1(1):37-41.

Miyata R, van Eeden SF. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter. Toxicology and applied pharmacology. 2011;257(2):209-26.

Vogelpoel LT, Hansen IS, Rispens T, Muller FJ, van Capel TM, Turina MC, et al. Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages. Nat Commun. 2014;5:5444.

Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD. Granulocyte-Macrophage Colony-Stimulating Factor (CSF) and Macrophage CSF-Dependent Macrophage Phenotypes Display Differences in Cytokine Profiles and Transcription Factor Activities: Implications for CSF Blockade in Inflammation. The Journal of Immunology. 2007;178(8):5245-52.

Fejer G, Wegner MD, Gyory I, Cohen I, Engelhard P, Voronov E, et al. Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(24):E2191-8.

Zhang X, Mosser DM. Macrophage activation by endogenous danger signals. J Pathol. 2008;214(2):161-78.

Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783-801.

Mosser DM. The many faces of macrophage activation. Journal of Leukocyte Biology. 2003;73(2):209-12.

Moresco EM, LaVine D, Beutler B. Toll-like receptors. Curr Biol. 2011;21(13):R488-93.

Saijo S, Iwakura Y. Dectin-1 and Dectin-2 in innate immunity against fungi. Int Immunol. 2011;23(8):467-72.

Scheller EL, Song J, Dishowitz MI, Hankenson KD, Krebsbach PH. A potential role for the myeloid lineage in leptin-regulated bone metabolism. Horm Metab Res. 2012;44(1):1-5.

Smeekens SP, van de Veerdonk FL, van der Meer JW, Kullberg BJ, Joosten LA, Netea MG. The Candida Th17 response is dependent on mannan- and beta-glucan-induced prostaglandin E2. International immunology. 2010;22(11):889-95.

Wind J, Smeekens S, Hanson J. Sucrose: metabolite and signaling molecule. Phytochemistry. 2010;71(14-15):1610-4.

Eder C. Mechanisms of interleukin-1beta release. Immunobiology. 2009;214(7):543-53.

Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov E, et al. IL-1alpha and IL-1beta recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol. 2011;187(9):4835-43.

Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1beta secretion. Cytokine Growth Factor Rev. 2011;22(4):189-95.

Postlethwait EM. Scavenger receptors clear the air. J Clin Invest. 2007;117(3):601-4.

Petrilli V, Papin S, Tschopp J. The inflammasome. Curr Biol. 2005;15(15):R581.

Geiger-Maor A, Levi I, Even-Ram S, Smith Y, Bowdish DM, Nussbaum G, et al. Cells exposed to sublethal oxidative stress selectively attract monocytes/macrophages via scavenger receptors and MyD88-mediated signaling. J Immunol. 2012;188(3):1234-44.

Ferracin LM, Fier CB, Vieira ML, Monteiro-Vitorello CB, Varani Ade M, Rossi MM, et al. Strain-specific polyketide synthase genes of Aspergillus niger. Int J Food Microbiol. 2012;155(3):137-45.

Ferreira de Oliveira JM, van Passel MW, Schaap PJ, de Graaff LH. Shotgun proteomics of Aspergillus niger microsomes upon D-xylose induction. Appl Environ Microbiol. 2010;76(13):4421-9.

Choe SI, Gravelat FN, Al Abdallah Q, Lee MJ, Gibbs BF, Sheppard DC. Role of Aspergillus niger acrA in arsenic resistance and its use as the basis for an arsenic biosensor. Appl Environ Microbiol. 2012;78(11):3855-63.

Ghosh S, Howe N, Volk K, Tati S, Nickerson KW, Petro TM. Candida albicans cell wall components and farnesol stimulate the expression of both inflammatory and regulatory cytokines in the murine RAW264.7 macrophage cell line. FEMS Immunol Med Microbiol. 2010;60(1):63-73.

Park SJ, Mehrad B. Innate immunity to Aspergillus species. Clin Microbiol Rev. 2009;22(4):535-51.

Dieudonne A, Torres D, Blanchard S, Taront S, Jeannin P, Delneste Y, et al. Scavenger receptors in human airway epithelial cells: role in response to double-stranded RNA. PLoS One. 2012;7(8):e41952.

Steele C, Rapaka RR, Metz A, Pop SM, Williams DL, Gordon S, et al. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog. 2005;1(4):e42.

Taramelli D, Malabarba MG, Sala G, Basilico N, Cocuzza G. Production of cytokines by alveolar and peritoneal macrophages stimulated by Aspergillus fumigatus conidia or hyphae. J Med Vet Mycol. 1996;34(1):49-56.

Gow NA, Netea MG, Munro CA, Ferwerda G, Bates S, Mora-Montes HM, et al. Immune recognition of Candida albicans beta-glucan by dectin-1. J Infect Dis. 2007;196(10):1565-71.

Kraal G, van der Laan LJ, Elomaa O, Tryggvason K. The macrophage receptor MARCO. Microbes and infection / Institut Pasteur. 2000;2(3):313-6.

Jozefowski S, Sulahian TH, Arredouani M, Kobzik L. Role of scavenger receptor MARCO in macrophage responses to CpG oligodeoxynucleotides. J Leukoc Biol. 2006;80(4):870-9.

Jozefowski S, Yang Z, Marcinkiewicz J, Kobzik L. Scavenger receptors and beta-glucan receptors participate in the recognition of yeasts by murine macrophages. Inflamm Res. 2012;61(2):113-26.


Refbacks

  • There are currently no refbacks.


Creative Commons License 
This work is licensed under a Creative Commons Attribution 3.0 License

ISSN 1754-2383 [Online] ©University of Plymouth