The overall goal of this Program Project Grant (P01) is to define the key interactions between multiple intracellular pathogens and infected host cells. Over the last 10 years, many of the host innate immune pathways involved in sensing microbial infection have been identified. The receptors controlling the activation of these pathways include the Toll-like receptors (TLRs) and a growing family of cytosolic receptors including Nods, Naips, Nalps, and multiple cytosolic nucleic acid sensors. Importantly, the contribution of each of these pathways during a microbial infection will differ based on the composition, lifestyle, and virulence mechanisms of that microbe. Core B of this P01 will maintain a colony of mouse strains with deficiencies in components of innate immunity or other genetic modifications useful for the study of innate immunity. Core B also supports an ENU-based forward genetic screen to identify new genes involved in host defense during L. monocytogenes, L. pneumophila, and M. tuberculosis infection. Mice and macrophages derived from these mice will be distributed to each of the projects within the P01. All mouse strains have been or will be backcrossed onto the C57B1/6 genetic background to equivalent degrees. Core B will reduce overall mouse costs due to economies of scale. In addition, each P01 project will benefit from using cells and mice with fewer genetic and experimental variations.
Core B will provide mice and cells lacking key immune genes to each of the projects within this P01 application. Experiments using these materials will dissect how the immune system detects and responds to a broad range of pathogens.
|Roberts, Allison W; Lee, Bettina L; Deguine, Jacques et al. (2017) Tissue-Resident Macrophages Are Locally Programmed for Silent Clearance of Apoptotic Cells. Immunity 47:913-927.e6|
|Whiteley, Aaron T; Ruhland, Brittany R; Edrozo, Mauna B et al. (2017) A Redox-Responsive Transcription Factor Is Critical for Pathogenesis and Aerobic Growth of Listeria monocytogenes. Infect Immun 85:|
|Lobingier, Braden T; Hüttenhain, Ruth; Eichel, Kelsie et al. (2017) An Approach to Spatiotemporally Resolve Protein Interaction Networks in Living Cells. Cell 169:350-360.e12|
|Portman, Jonathan L; Huang, Qiongying; Reniere, Michelle L et al. (2017) Activity of the Pore-Forming Virulence Factor Listeriolysin O Is Reversibly Inhibited by Naturally Occurring S-Glutathionylation. Infect Immun 85:|
|Fu, Juan; Sen, Rupashree; Masica, David L et al. (2017) Autologous reconstitution of human cancer and immune system in vivo. Oncotarget 8:2053-2068|
|Barry, Kevin C; Ingolia, Nicholas T; Vance, Russell E (2017) Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen. Elife 6:|
|Tenthorey, Jeannette L; Haloupek, Nicole; López-Blanco, José Ramón et al. (2017) The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion. Science 358:888-893|
|Deguine, Jacques; Wei, Jessica; Barbalat, Roman et al. (2017) Local TNFR1 Signaling Licenses Murine Neutrophils for Increased TLR-Dependent Cytokine and Eicosanoid Production. J Immunol 198:2865-2875|
|Ekiert, Damian C; Bhabha, Gira; Isom, Georgia L et al. (2017) Architectures of Lipid Transport Systems for the Bacterial Outer Membrane. Cell 169:273-285.e17|
|Mitchell, Gabriel; Isberg, Ralph R (2017) Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation. Cell Host Microbe 22:166-175|
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