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.
|Koch, Meghan A; Reiner, Gabrielle L; Lugo, Kyler A et al. (2016) Maternal IgG and IgA Antibodies Dampen Mucosal T Helper Cell Responses in Early Life. Cell 165:827-41|
|Burke, Thomas P; Portnoy, Daniel A (2016) SpoVG Is a Conserved RNA-Binding Protein That Regulates Listeria monocytogenes Lysozyme Resistance, Virulence, and Swarming Motility. MBio 7:e00240|
|Newman, Zachary R; Young, Janet M; Ingolia, Nicholas T et al. (2016) Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9. Proc Natl Acad Sci U S A 113:E1362-71|
|Mitchell, Gabriel; Chen, Chen; Portnoy, Daniel A (2016) Strategies Used by Bacteria to Grow in Macrophages. Microbiol Spectr 4:|
|Sanman, Laura E; Qian, Yu; Eisele, Nicholas A et al. (2016) Disruption of glycolytic flux is a signal for inflammasome signaling and pyroptotic cell death. Elife 5:e13663|
|Rauch, Isabella; Tenthorey, Jeannette L; Nichols, Randilea D et al. (2016) NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. J Exp Med 213:657-65|
|Mitchell, Gabriel; Ge, Liang; Huang, Qiongying et al. (2015) Avoidance of autophagy mediated by PlcA or ActA is required for Listeria monocytogenes growth in macrophages. Infect Immun 83:2175-84|
|Coady, Alison; Sil, Anita (2015) MyD88-dependent signaling drives host survival and early cytokine production during Histoplasma capsulatum infection. Infect Immun 83:1265-75|
|McKay, Susannah L; Portnoy, Daniel A (2015) Ribosome hibernation facilitates tolerance of stationary-phase bacteria to aminoglycosides. Antimicrob Agents Chemother 59:6992-9|
|Siegrist, M Sloan; Aditham, Arjun K; Espaillat, Akbar et al. (2015) Host actin polymerization tunes the cell division cycle of an intracellular pathogen. Cell Rep 11:499-507|
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