Model-based Investigation of the Proinflammatory Microenvironment and Response to Gram-negative Bacteria

Intracellular pathogens like Francisella tularensis (Ft), a gram-negative Class A biothreat agent can trigger the release of cytokines, chemokines, and effector molecules into the microenvironment surrounding the infected cell, contributing to the formation of a proinflammatory microenvironment (PME). Immune cells recruited into the PME can be primed and activated by cytokine exposure promoting a more robust interaction between infiltrating immune cells and infected cells or, in the case of phagocytic cells, priming the cell to more effectively eliminate subsequent Ft infection. Macrophages and NK cells are central to the innate immune response to Ft and primary producers of TNF-α and IFN-γ, respective. Focusing on these key PME cytokines, which are found to modulate the in vivo response to Ft, we developed in silico and in vitro models to investigate the role of PME in macrophage activation and outcome of infection. For more information see: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153289 The Interplay between the Human Microbiome and Respiratory Viruses: A Multi-scale Story of Influenza and COVID-19 Christian Forst Icahn School of Medicine at Mount Sinai The ongoing SARS-CoV-2 pandemic poses a threat to public health and economy, thus urges the scientific community to join efforts in the search of cures. Meanwhile, both influenza and COVID-19 are respiratory diseases caused by airborne RNA viruses. Microbes in the respiratory system have been proven to contribute to the outcome of the diseases. However, scientific advances from studying influenza infection have potentials to benefit the search of cure for SARS-CoV-2 infections. Here we present a comprehensive, multi-scale network analysis of the systems response to the virus. We have developed methods that integrate single-cell and bulk transcriptomic data. These integrated data were further related to the microbiome and clinical outcomes. By this approach we were able to identify cell-population specific key-regulators and host-processes that are hijacked by the virus for its advantage and that contribute to the severity of these infectious diseases. For more information see: https://link.springer.com/article/10.1186/s40168-020-00803-2 *Contents* 00:00 - Introduction 03:58 - Presentation--Elebeoba May: Model-based Investigation of the Proinflammatory Microenvironment and Response to Gram-negative Bacteria 26:08 - Questions and Answers 30:20 - Presentation--Christian Forst: The Interplay between the Human Microbiome and Respiratory Viruses: A Multi-scale Story of Influenza and COVID-19 1:03:24 - Questions and Answers If you found this video useful, please check out our other videos on computational modeling, infection and immunology: https://youtube.com/playlist?list=PLiEtieOeWbMKh9VcQoinSwODcSZKMTGat Please consider joining our IMAG/MSM WG on Multiscale Modeling and Viral Pandemics: https://www.imagwiki.nibib.nih.gov/content/msm-viral-pandemics-meetings Please also consider joining the Global Alliance for Immune Prediction and Intervention: http://glimprint.org/