Varying Inoculum Dose to Assess the Roles of the Immune Response and Target Cell Depletion by the Pathogen in Control of Acute Viral Infections
Autor: | Balaji Manicassamy, Rustom Antia, James R Moore, Hasan Ahmed, Adolfo García-Sastre, Andreas Handel |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
General Mathematics Immunology Cell Biology Adaptive Immunity General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Immune system Orthomyxoviridae Infections medicine Animals Humans Gene Pathogen General Environmental Science Pharmacology Innate immune system Lung Host Microbial Interactions Mechanism (biology) General Neuroscience Models Immunological Mathematical Concepts Viral Load Immunity Innate Disease Models Animal 030104 developmental biology medicine.anatomical_structure Computational Theory and Mathematics Virus Diseases 030220 oncology & carcinogenesis General Agricultural and Biological Sciences Infectious agent |
Zdroj: | Bulletin of mathematical biology. 82(3) |
ISSN: | 1522-9602 |
Popis: | It is difficult to determine whether an immune response or target cell depletion by the infectious agent is most responsible for the control of acute primary infection. Both mechanisms can explain the basic dynamics of an acute infection-exponential growth of the pathogen followed by control and clearance-and can also be represented by many different differential equation models. Consequently, traditional model comparison techniques using time series data can be ambiguous or inconclusive. We propose that varying the inoculum dose and measuring the subsequent infectious load can rule out target cell depletion by the pathogen as the main control mechanism. Infectious load can be any measure that is proportional to the number of infected cells, such as viraemia. We show that a twofold or greater change in infectious load is unlikely when target cell depletion controls infection, regardless of the model details. Analyzing previously published data from mice infected with influenza, we find the proportion of lung epithelial cells infected was 21-fold greater (95% confidence interval 14-32) in the highest dose group than in the lowest. This provides evidence in favor of an alternative to target cell depletion, such as innate immunity, in controlling influenza infections in this experimental system. Data from other experimental animal models of acute primary infection have a similar pattern. |
Databáze: | OpenAIRE |
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