Faculty Research Page

Greg Barton

Greg Barton

Class of ’36 Endowed Chair and Professor of Immunology and Pathogenesis

Lab Homepage: http://www.thebartonlab.com/

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Research Interests

Our group studies innate immunity with the goal of understanding strategies of pathogen recognition and self/non-self discrimination. The innate immune system represents the ideal vehicle to pursue these questions because it has evolved under constant selective pressure from microbial pathogens. While adaptive immunity utilizes millions of clonally expressed receptors, the innate immune system uses an alternative strategy: a limited number of receptors with fixed specificities that are expressed non-clonally. The benefit of this strategy is speed; the cost is that the system is critically dependent on the selection of appropriate microbial targets. If the target is easily mutated, then the immune response will fail. If the target is not unique to microbes, then the immune response may attack the host. The solutions to this problem represent a fascinating set of compromises by both the host and microbes. We believe that studying this balance between innate immunity and microbial pathogens will reveal critical balance points in self/non-self discrimination with fundamental implications for our understanding of mammalian immunity. To tackle these issues the lab focuses on the function and regulation of Toll-like receptors (TLRs). TLRs are the prototypical innate immune receptor family. They participate in innate immunity, adaptive immunity, and, in some instances, autoimmunity. This central role makes TLRs an ideal system to address the conceptual issues discussed above.

Current Projects

The lab works in a number of areas, all focused on aspects of innate immunity:

  • The function, signal transduction pathways, and regulation of innate immune receptors.
  • The role of innate immune receptors in autoimmune disease.
  • Strategies of pathogen recognition by innate immune receptors.
  • Coevolution of host-pathogen interactions.
  • Intestinal immunity

Selected Publications

Majer O*, Liu B*, Kreuk LSM, Krogan N, Barton GM. Unc93b1 recruits Syntenin-1 to dampen TLR7 signaling and prevent autoimmunity. Nature (2019) 575:366-370. *equal contribution

Majer O, Liu B, Woo BJ, Kreuk LSM, Van Dis E, Barton GM. Release from Unc93b1 reinforces compartmentalized activation of select Toll-like receptors. Nature (2019) 575:371-374.

Kreuk LSM, Koch MA, Slayden LC, Lind NA, Chu S, Savage HP, Kantor AB, Baumgarth N, Barton GM. B cell receptor and TLR signaling coordinate to control distinct B-1 responses to both self and the microbiota. eLife (2019) 8:e47015.

Ansaldo E, Slayden LC, Ching KL, Koch MA, Wolf NK, Plichta DR, Brown EM, Graham DB, Xavier RJ, Moon JJ, Barton GM. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science (2019) 364:1179-1184.

Price AE, Shamardani K, Lugo KA, Deguine J, Roberts AW, Lee BL, Barton GM. Reporter mice reveal spatial patterns of Toll-like receptor expression and function in intestinal epithelial cells. Immunity (2018) 49:560-575.

Roberts AW, Lee BL, Deguine J, John S, Shlomchik MJ, Barton GM. Resident Macrophages are Locally Programmed for Silent Clearance of Apoptotic Cells. Immunity (2017) 47:913-927.

Koch MA, Reiner GL, Lugo KA, Kreuk LS, Stanbery AG, Ansaldo E, Seher TD, Ludington WB, Barton GM. Maternal IgG and IgA Antibodies Dampen Mucosal T Helper Cell Responses in Early Life. Cell (2016) 165:827-841.

Newman ZR, Young JM, Ingolia NT, Barton GM. Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9. PNAS USA (2016) 113:E1362-1371.

Sivick KE, Arpaia N, Reiner GL, Lee BL, Russell BR, Barton GM. Toll-like Receptor-Deficient Mice Reveal How Innate Immune Signaling Influences Salmonella Virulence Strategies. Cell Host Microbe (2014) 15: 203-213.

Deguine J, Lee BL, Newman Z, Barton GM. No antigen presentation defect in Unc93b13d/3d (3d) mice. Nature Immunology (2013) 14:1101-1102.

Lee BL, Moon JE, Shu JH, Yuan L, Newman ZR, Schekman R, Barton GM. UNC93B1 mediates differential trafficking of endosomal TLRs. eLife (2013) 2:e00291.

Mouchess ML, Arpaia N, Souza G, Barbalat R, Ewald SE, Lau L, Barton GM. Transmembrane mutations in Toll-like Receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation. Immunity, (2011) 35:1-12.

Arpaia N, Godec J, Lau L, Sivick KE, McLaughlin LM, Jones MB, Dracheva T, Peterson SN, Monack DM, Barton GM. TLR signaling is required for virulence of an intracellular pathogen. Cell (2011) 144:675-688.

Barbalat R, Lau L, Locksley RM, and Barton GM.  Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nature Immunology (2009) 10:1200-1207.

Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi G-P, Chapman HA, and Barton GM. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature (2008) 456:658-662.

Photo Credit: Mark Hanson of Mark Joseph Studios

Last Updated 2020-09-10