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Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

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Related in: MedlinePlus

Experimental evidence for the effect of Abs, CTLs, and IFN.Published viral titer time courses for influenza infection in normal (solid) or immunocompromised (dashed) mice (or pigs in Seo) where either the Abs (left column), CTLs (centre column), or IFN (right column) responses were individually compromised by various means (e.g., toxins, antisera, knock-out). Data extracted from Iwasaki [11], Neff-LaFord [70] Kris [66], Wells [67], Yap [118], Garcia-Sastre [68], Hoshino [25], and Seo [13].
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pone-0057088-g002: Experimental evidence for the effect of Abs, CTLs, and IFN.Published viral titer time courses for influenza infection in normal (solid) or immunocompromised (dashed) mice (or pigs in Seo) where either the Abs (left column), CTLs (centre column), or IFN (right column) responses were individually compromised by various means (e.g., toxins, antisera, knock-out). Data extracted from Iwasaki [11], Neff-LaFord [70] Kris [66], Wells [67], Yap [118], Garcia-Sastre [68], Hoshino [25], and Seo [13].

Mentions: In animal models, the effect of individual components of the immune response on the course and outcome of the infection can be evaluated by down-regulating or neutralizing a specific component of the immune response or its activity. These studies use component-specific antisera [11], [25], genetic modification (knock-out) [13], [66]–[69], or treatment with toxins [70]. Unfortunately, these manipulations sometimes do not fully remove the immune component [25], [67], [71] or removal of the component also affects other components of the immune response [11], [72]. Additionally, the immune response in these animal models might not be representative of that of a human host [28], [29]. Despite these shortcomings, experiments in animals can help shape our understanding of the relative role of different immune components. Published results of these experiments conducted in mice (with the exception of Seo [13], which was conducted in pigs) are assembled in Fig. 2 where graphs show the viral titer time course for an influenza infection with a full immune response or with one immune component disabled or destroyed.


Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Experimental evidence for the effect of Abs, CTLs, and IFN.Published viral titer time courses for influenza infection in normal (solid) or immunocompromised (dashed) mice (or pigs in Seo) where either the Abs (left column), CTLs (centre column), or IFN (right column) responses were individually compromised by various means (e.g., toxins, antisera, knock-out). Data extracted from Iwasaki [11], Neff-LaFord [70] Kris [66], Wells [67], Yap [118], Garcia-Sastre [68], Hoshino [25], and Seo [13].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585335&req=5

pone-0057088-g002: Experimental evidence for the effect of Abs, CTLs, and IFN.Published viral titer time courses for influenza infection in normal (solid) or immunocompromised (dashed) mice (or pigs in Seo) where either the Abs (left column), CTLs (centre column), or IFN (right column) responses were individually compromised by various means (e.g., toxins, antisera, knock-out). Data extracted from Iwasaki [11], Neff-LaFord [70] Kris [66], Wells [67], Yap [118], Garcia-Sastre [68], Hoshino [25], and Seo [13].
Mentions: In animal models, the effect of individual components of the immune response on the course and outcome of the infection can be evaluated by down-regulating or neutralizing a specific component of the immune response or its activity. These studies use component-specific antisera [11], [25], genetic modification (knock-out) [13], [66]–[69], or treatment with toxins [70]. Unfortunately, these manipulations sometimes do not fully remove the immune component [25], [67], [71] or removal of the component also affects other components of the immune response [11], [72]. Additionally, the immune response in these animal models might not be representative of that of a human host [28], [29]. Despite these shortcomings, experiments in animals can help shape our understanding of the relative role of different immune components. Published results of these experiments conducted in mice (with the exception of Seo [13], which was conducted in pigs) are assembled in Fig. 2 where graphs show the viral titer time course for an influenza infection with a full immune response or with one immune component disabled or destroyed.

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

Show MeSH
Related in: MedlinePlus