In vivo-to-in silico iterations to investigate aeroallergen-host interactions.
BACKGROUND
Allergic asthma is a complex process arising out of the interaction between the immune system and aeroallergens. Yet, the relationship between aeroallergen exposure, allergic sensitization and disease remains unclear. This knowledge is essential to gain further insight into the origin and evolution of allergic diseases. The objective of this research is to develop a computational view of the interaction between aeroallergens and the host by investigating the impact of dose and length of aeroallergen exposure on allergic sensitization and allergic disease outcomes, mainly airway inflammation and to a lesser extent lung dysfunction and airway remodeling.


RESULTS
BALB/C mice were exposed intranasally to a range of concentrations of the most pervasive aeroallergen worldwide, house dust mite (HDM), for up to a quarter of their lifespan (20 weeks). Actual biological data delineating the kinetics, nature and extent of responses for local (airway inflammation) and systemic (HDM-specific immunoglobulins) events were obtained. Mathematical equations for each outcome were developed, evaluated, refined through several iterations involving in vivo experimentation, and validated. The models accurately predicted the original biological data and simulated an extensive array of previously unknown responses, eliciting two- and three-dimensional models. Our data demonstrate the non-linearity of the relationship between aeroallergen exposure and either allergic sensitization or airway inflammation, identify thresholds, behaviours and maximal responsiveness for each outcome, and examine inter-variable relationships.


CONCLUSIONS
This research provides a novel way to visualize allergic responses in vivo and establishes a basic experimental platform upon which additional variables and perturbations can be incorporated into the system.
Llop-Guevara
Alba
A
Department of Pathology and Molecular Medicine, Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
Colangelo
Marc
M
Chu
Derek K
DK
Moore
Cheryl Lynn
CL
Stieber
Nicole A
NA
Walker
Tina D
TD
Goncharova
Susanna
S
Coyle
Anthony J
AJ
Lundblad
Lennart K A
LK
O'Byrne
Paul M
PM
Lovric
Miroslav
M
Jordana
Manel
M
D000393:Air Pollutants / Q000633:toxicity*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004391:Dust; D005260:Female; D006967:Hypersensitivity / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008925:Mites / Q000276:immunology*
D000393:Air Pollutants; D000485:Allergens; D004391:Dust