DOI: 10.1097/01.ccm.0000474270.63682.95
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Issn Print: 0090-3493
Publication Date: 2015/12/01
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Excerpt
Methods: Two groups of BALB/c mice (age 12–16 wks and 72–76 wks) were infected at 2 inocula: a survivable 50 PFU dose and a lethal 500 PFU dose. Data were measured at 10 points over 19 days in the sublethal and 6 points over 7 days in the lethal, after which all mice had died. We developed a Boolean model to describe the interactions between virus and 21 immune components including cells, chemokines, and cytokines from innate and adaptive immunity. Each age group has its own set of rules using Boolean operators to describe the complex series of interactions that activate and deactivate immune components.
Results: Our model accurately simulates the immune response for both ages and both inocula included in the data (95% accurate for younger mice, 94% accurate for older mice). Data varies primarily in the onset of immunity, particularly the inflammatory response, which leads to a 2 day delay in clearance of the virus from the aged host in the sublethal cohort. Most rules governing behavior of innate immunity components differ between young and old mice, in accord with experiments, which show distinct temporal patterns for cytokines and chemokines between age groups. Rules for infected cells, NK cells, and CTLs are constant between ages, however.
Conclusions: Discrete, rule-based models allow the data-driven discovery of important interactions between components of host-virus response to influenza infection. Although there is overlap, many of the rules driving the immune response to influenza are distinct between young and older hosts, possibly suggesting that immunomodulatory strategies should be age-dependent.
