5 years ago

Discrete dynamical modeling of influenza infection suggests age-dependent differences in immunity.

Matuszewski M, Ermentrout GB, Clermont G, Parker RS, Keef E, Urbano A, Toapanta FR, Swigon D, Ross TM, Zhang LA
Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and greater likelihood of death. Our study applies a rule-based model to infer which components of immune response are most changed in an aged host. 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 case and 6 points over 7 days in the lethal case, after which all mice had died. 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 older host in the sublethal cohort. 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. The model identifies distinct sets of rules for each age group using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. 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), and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus.Importance Influenza virus infection causes high morbidity and mortality every year, especially in the elderly. The elderly tend to have delayed onset of many immune responses, as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the intra-host immune response to influenza viral infection. The model is fit to experimental data for young and older mice infected with influenza. We generated distinct sets of rules for each age group to capture the temporal differences seen in the immune responses of these mice. These rules describe a network of interactions leading to either clearance of the virus or death of the host, depending on the initial dosage of virus. Our models clearly demonstrate the differences in these two age groups, particularly in the innate immune responses.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28904202

DOI: PubMed:28904202

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.