دورية أكاديمية
A computational model of invasive aspergillosis in the lung and the role of iron.
| العنوان: | A computational model of invasive aspergillosis in the lung and the role of iron. |
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| المؤلفون: | Oremland M; Mathematical Biosciences Institute, Ohio State University, 1735 Neil Ave, Columbus OH, USA. oremland.2@osu.edu., Michels KR; University of Virginia, Pulmonary and Critical Care Medicine, Charlottesville VA, USA., Bettina AM; University of Virginia, Pulmonary and Critical Care Medicine, Charlottesville VA, USA., Lawrence C; Virginia Bioinformatics Institute, Virginia Tech, 1015 Life Science Circle, Blacksburg VA, USA., Mehrad B; University of Virginia, Pulmonary and Critical Care Medicine, Charlottesville VA, USA., Laubenbacher R; Center for Quantitative Medicine, University of Connecticut Health Center, 236 Farmington Ave, Farmington CT, USA.; Jackson Laboratory for Genomic Medicine, 236 Farmington Ave, Farmington CT, USA. |
| المصدر: | BMC systems biology [BMC Syst Biol] 2016 Apr 21; Vol. 10, pp. 34. Date of Electronic Publication: 2016 Apr 21. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101301827 Publication Model: Electronic Cited Medium: Internet ISSN: 1752-0509 (Electronic) Linking ISSN: 17520509 NLM ISO Abbreviation: BMC Syst Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central |
| مواضيع طبية MeSH: | Computer Simulation*, Aspergillosis/*metabolism , Iron/*metabolism , Lung/*metabolism , Lung/*microbiology, Animals ; Female ; Lung/pathology ; Mice ; Models, Biological |
| مستخلص: | Background: Invasive aspergillosis is a severe infection of immunocompromised hosts, caused by the inhalation of the spores of the ubiquitous environmental molds of the Aspergillus genus. The innate immune response in this infection entails a series of complex and inter-related interactions between multiple recruited and resident cell populations with each other and with the fungal cell; in particular, iron is critical for fungal growth. Results: A computational model of invasive aspergillosis is presented here; the model can be used as a rational hypothesis-generating tool to investigate host responses to this infection. Using a combination of laboratory data and published literature, an in silico model of a section of lung tissue was generated that includes an alveolar duct, adjacent capillaries, and surrounding lung parenchyma. The three-dimensional agent-based model integrates temporal events in fungal cells, epithelial cells, monocytes, and neutrophils after inhalation of spores with cellular dynamics at the tissue level, comprising part of the innate immune response. Iron levels in the blood and tissue play a key role in the fungus' ability to grow, and the model includes iron recruitment and consumption by the different types of cells included. Parameter sensitivity analysis suggests the model is robust with respect to unvalidated parameters, and thus is a viable tool for an in silico investigation of invasive aspergillosis. Conclusions: Using laboratory data from a mouse model of invasive aspergillosis in the context of transient neutropenia as validation, the model predicted qualitatively similar time course changes in fungal burden, monocyte and neutrophil populations, and tissue iron levels. This model lays the groundwork for a multi-scale dynamic mathematical model of the immune response to Aspergillus species. |
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| معلومات مُعتمدة: | HL098329 United States HL NHLBI NIH HHS; HL098526 United States HL NHLBI NIH HHS; R01 HL098329 United States HL NHLBI NIH HHS; R21 AI117397 United States AI NIAID NIH HHS; R21 AI101619 United States AI NIAID NIH HHS; 1R21AI101619-01 United States AI NIAID NIH HHS; T32 AI007046 United States AI NIAID NIH HHS; R01 HL098526 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: Agent-based model; Invasive aspergillosis; Iron; Lung |
| المشرفين على المادة: | E1UOL152H7 (Iron) |
| تواريخ الأحداث: | Date Created: 20160422 Date Completed: 20170222 Latest Revision: 20181113 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC4839115 |
| DOI: | 10.1186/s12918-016-0275-2 |
| PMID: | 27098278 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1752-0509 |
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| DOI: | 10.1186/s12918-016-0275-2 |