Class of ’36 Endowed Chair and Professor of Immunology and PathogenesisLab Homepage: http://www.thebartonlab.com/
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.
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
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.
Arpaia N and Barton GM. The impact of Toll-like receptors on bacterial virulence strategies. Current Opinion in Microbiology (2013) 16:17-22.
Arpaia N and Barton GM. Toll-like receptors: key players in antiviral immunity. Current Opinion in Virology (2012) 1:447-454.
*Chiang CY, *Engel A, *Opaluch AM, Ramos I, Maestre AM, Secundino I, De Jesus PD, Nguyen QT, Welch G, Bonamy GM, Miraglia LJ, Orth AP, Nizet V, Fernandez-Sesma A, Zhou Y, Barton GM, Chanda SK. Cofactors required for TLR7- and TLR9-dependent innate immune responses. Cell Host Microbe (2012) 11:306-318. *These authors contributed equally.
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.
Pezda AC, Penn A, Barton GM, Coscoy L. Suppression of TLR9 immunostimulatory motifs in the genome of a gammaherpesvirus. J Immunol. (2011) 187:887-96.
Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. Journal of Experimental Medicine (2011) 208:643-651.
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. [PMID: 21376231].
Ewald S and Barton GM. Nucleic acid sensing Toll-like receptors in autoimmunity. Current Opinion in Immunology (2011) 23:3-9. [PMID: 21146971]
*Barbalat R, *Ewald SE, *Mouchess ML, Barton GM. Nucleic acid recognition by the innate immune system. Annual Review of Immunology, Vol. 29 (2011). *These authors contributed equally. [PMID: 21219183]
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. [PMID: 19801985]
Barton GM & Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nature Reviews Immunology (2009) 9:535-542. [PMID: 19556980]
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. [PMID: 18820679]
Barton GM. A Calculated Response: Control of Inflammation by the Innate Immune System. The Journal of Clinical Investigation (2008) 118:413-420. [PMID: 18246191]
Photo Credit: Mark Hanson of Mark Joseph Studios
Last Updated 2013-08-26