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Modeling Systems-Level Regulation of Host Immune Responses

Summary: Modeling Systems-Level Regulation
of Host Immune Responses
Juilee Thakar1
, Mylisa Pilione2
, Girish Kirimanjeswara2
, Eric T. Harvill2
, ReŽka Albert1*
1 Department of Physics, Pennsylvania State University, University Park, Pennsylvania, United States of America, 2 Department of Veterinary and Biomedical Sciences,
Pennsylvania State University, University Park, Pennsylvania, United States of America
Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune
responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or
of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host
immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental
information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by
comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model
indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the
most active immune processes. We compare and discuss the effect of the species-specific virulence factors on
disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our
model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary
infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the


Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University


Collections: Biology and Medicine