Nutritional Lung Immunity

A description of mathematical models related to the monocyte derived macrophages.

Modeling iron handling by monocyte derived macrophages challenged by A. fumigatus

Iron is essential for all living organisms. A characteristic immune response to infections is the sequestration of iron by macrophages to keep it away from pathogens. We have created a generalized Boolean model of how monocyte derived activate an iron metabolism program after sensing A. fumigatus based on the transcriptomics data (see the Bioinformatics section) as well as the literature.

Wiring diagram

The code for the implementation of the intracellular model, as well as a more thorough description can be found here.

Bibliography

  • Toledano, V., Hernández-Jiménez, E., Cubillos-Zapata, C., Flandez, M., Álvarez, E., Varela-Serrano, A., Cantero, R., Valles, G., García-Rio, F., & López-Collazo, E. (2015). Galactomannan Downregulates the Inflammation Responses in Human Macrophages via NFκB2/P100. Mediators of Inflammation, 2015, 942517. https://doi.org/10.1155/2015/942517
  • Beaumont, C. (2010). Multiple Regulatory Mechanisms Act in Concert to Control Ferroportin Expression and Heme Iron Recycling by Macrophages. Haematologica, 95(8), 1233–1236. https://doi.org/10.3324/haematol.2010.025585
  • Heinekamp, T., Schmidt, H., Lapp, K., Pähtz, V., Shopova, I., Köster-Eiserfunke, N., Krüger, T., Kniemeyer, O., & Brakhage, A. A. (2015). Interference of Aspergillus Fumigatus with the Immune Response. Seminars in Immunopathology, 37(2), 141–152. https://doi.org/10.1007/s00281-014-0465-1
  • Hope, W. W., Petraitis, V., Petraitiene, R., Aghamolla, T., Bacher, J., & Walsh, T. J. (2010). The Initial 96 Hours of Invasive Pulmonary Aspergillosis: Histopathology, Comparative Kinetics of Galactomannan and (1->3) β-d-Glucan and Consequences of Delayed Antifungal Therapy. Antimicrobial Agents and Chemotherapy, 54(11), 4879–4886. https://doi.org/10.1128/AAC.00673-10
  • Kemna, E., Pickkers, P., Nemeth, E., van der Hoeven, H., & Swinkels, D. (2005). Time-Course Analysis of Hepcidin, Serum Iron, and Plasma Cytokine Levels in Humans Injected with LPS. Blood, 106(5), 1864–1866. https://doi.org/10.1182/blood-2005-03-1159
  • Lee, P., Peng, H., Gelbart, T., Wang, L., & Beutler, E. (2005). Regulation of Hepcidin Transcription by Interleukin-1 and Interleukin-6. Proceedings of the National Academy of Sciences of the United States of America, 102(6), 1906–1910. https://doi.org/10.1073/pnas.0409808102
  • Liu, Z., Lanford, R., Mueller, S., Gerhard, G. S., Luscieti, S., Sanchez, M., & Devireddy, L. (2012). Siderophore-Mediated Iron Trafficking in Humans Is Regulated by Iron. Journal of Molecular Medicine (Berlin, Germany), 90(10), 1209–1221. https://doi.org/10.1007/s00109-012-0899-7
  • Miller, L. L., Miller, S. C., Torti, S. V., Tsuji, Y., & Torti, F. M. (1991). Iron-Independent Induction of Ferritin H Chain by Tumor Necrosis Factor. Proceedings of the National Academy of Sciences of the United States of America, 88(11), 4946–4950. https://doi.org/10.1073/pnas.88.11.4946
  • Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M. V., Ganz, T., & Kaplan, J. (2004). Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization. Science (New York, N.Y.), 306(5704), 2090–2093. https://doi.org/10.1126/science.1104742
  • Pantopoulos, K. (2004). Iron Metabolism and the IRE/IRP Regulatory System: An Update. Annals of the New York Academy of Sciences, 1012, 1–13. https://doi.org/10.1196/annals.1306.001
  • Philippe, B., Ibrahim-Granet, O., Prévost, M. C., Gougerot-Pocidalo, M. A., Sanchez Perez, M., Van der Meeren, A., & Latgé, J. P. (2003). Killing of Aspergillus Fumigatus by Alveolar Macrophages Is Mediated by Reactive Oxidant Intermediates. Infection and Immunity, 71(6), 3034–3042. https://doi.org/10.1128/iai.71.6.3034-3042.2003
  • Seifert, M., Nairz, M., Schroll, A., Schrettl, M., Haas, H., & Weiss, G. (2008). Effects of the Aspergillus Fumigatus Siderophore Systems on the Regulation of Macrophage Immune Effector Pathways and Iron Homeostasis. Immunobiology, 213(9-10), 767–778. https://doi.org/10.1016/j.imbio.2008.07.010
  • Soares, M. P., & Hamza, I. (2016). Macrophages and Iron Metabolism [Journal Article]. Immunity, 44(3), 492–504. https://doi.org/10.1016/j.immuni.2016.02.016
  • Steele, C., Rapaka, R. R., Metz, A., Pop, S. M., Williams, D. L., Gordon, S., Kolls, J. K., & Brown, G. D. (2005). The Beta-Glucan Receptor Dectin-1 Recognizes Specific Morphologies of Aspergillus Fumigatus. PLoS Pathogens, 1(4), e42. https://doi.org/10.1371/journal.ppat.0010042
  • Thomsen, J. H., Etzerodt, A., Svendsen, P., & Moestrup, S. K. (2013). The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging. Oxidative Medicine and Cellular Longevity, 2013, 523652. https://doi.org/10.1155/2013/523652
  • Tolosano, E., & Altruda, F. (2002). Hemopexin: Structure, Function, and Regulation. DNA and Cell Biology, 21(4), 297–306. https://doi.org/10.1089/104454902753759717
  • Tomee, J. F., & van der Werf, T. S. (2001). Pulmonary Aspergillosis. The Netherlands Journal of Medicine, 59(5), 244–258. https://doi.org/10.1016/s0300-2977(01)00163-2
  • Tsuji, Y., Miller, L. L., Miller, S. C., Torti, S. V., & Torti, F. M. (1991). Tumor Necrosis Factor-Alpha and Interleukin 1-Alpha Regulate Transferrin Receptor in Human Diploid Fibroblasts. Relationship to the Induction of Ferritin Heavy Chain. The Journal of Biological Chemistry, 266(11), 7257–7261.
  • Vela, D. (2018). Hepcidin, an Emerging and Important Player in Brain Iron Homeostasis. Journal of Translational Medicine, 16(1), 25. https://doi.org/10.1186/s12967-018-1399-5
  • Vethanayagam, R. R., Almyroudis, N. G., Grimm, M. J., Lewandowski, D. C., Pham, C. T. N., Blackwell, T. S., Petraitiene, R., Petraitis, V., Walsh, T. J., Urban, C. F., & Segal, B. H. (2011). Role of NADPH Oxidase versus Neutrophil Proteases in Antimicrobial Host Defense. PLOS ONE, 6(12), e28149. https://doi.org/10.1371/journal.pone.0028149
  • Vijayan, V., Wagener, F. A. D. T. G., & Immenschuh, S. (2018). The Macrophage Heme-Heme Oxygenase-1 System and Its Role in Inflammation. Biochemical Pharmacology, 153, 159–167. https://doi.org/10.1016/j.bcp.2018.02.010
  • Wang, C.-Y., Jenkitkasemwong, S., Duarte, S., Sparkman, B. K., Shawki, A., Mackenzie, B., & Knutson, M. D. (2012). ZIP8 Is an Iron and Zinc Transporter Whose Cell-Surface Expression Is up-Regulated by Cellular Iron Loading. The Journal of Biological Chemistry, 287(41), 34032–34043. https://doi.org/10.1074/jbc.M112.367284
  • Wrighting, D. M., & Andrews, N. C. (2006). Interleukin-6 Induces Hepcidin Expression through STAT3. Blood, 108(9), 3204–3209. https://doi.org/10.1182/blood-2006-06-027631
  • Zmeili, O. S., & Soubani, A. O. (2007). Pulmonary Aspergillosis: A Clinical Update. QJM: Monthly Journal of the Association of Physicians, 100(6), 317–334. https://doi.org/10.1093/qjmed/hcm035