Death receptor 3 is essential for generating optimal protective CD41 T-cell immunity against Salmonella

Buchan, Sarah L., Taraban, Vadim Y., Slebioda, Tomasz J., James, Sonya, Cunningham, Adam F. and Al-Shamkhani, Aymen (2012) Death receptor 3 is essential for generating optimal protective CD41 T-cell immunity against Salmonella. European Journal of Immunology, 42, (3), 580-588. (doi:10.1002/eji.201041950). (PMID:22259035).


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The TNF receptor superfamily member death receptor 3 (DR3) exacerbates Th2- and Th17-cell-mediated inflammatory and autoimmune conditions, yet no role in host defence has been reported. Here, we examined the role of DR3 during infection with Salmonella enterica serovar Typhimurium. Infection resulted in protracted expression of the DR3 ligand TL1A but not the related TNF superfamily proteins OX40L or CD30L. TL1A expression was localized to splenic F4/80+ macrophages where S. enterica Typhimurium replicates, and temporally coincided with the onset of CD4+-cell expansion. To address the relevance of the TL1A-DR3 interaction, we examined immune responses to S. enterica Typhimurium in mice lacking DR3. Infected DR3-/- mice harboured reduced numbers of antigen-experienced and proliferating CD4+ T cells compared with WT mice. Furthermore, the frequency of IFN-?+ CD4+ T cells in DR3-/- mice was lower throughout the time of bacterial clearance. Importantly, bacterial clearance, which is dependent on Th1 cells, was also impaired in DR3-/- mice. This defect was intrinsic to CD4+ T cells as evidenced by an increase in bacterial burden in RAG2-deficient mice receiving DR3-/- CD4+ T cells compared with WT CD4+-cell recipients. These data establish for the first time a role for DR3 in a host defence responce.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1002/eji.201041950
ISSNs: 0014-2980 (print)
1521-4141 (electronic)
Keywords: costimulation, DR3, Th1 cells, TNF receptor superfamily, TNFRSF25
Subjects: Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Medicine > Cancer Sciences
ePrint ID: 339281
Date :
Date Event
March 2012Published
19 January 2012Made publicly available
16 November 2011Accepted
Date Deposited: 25 May 2012 11:40
Last Modified: 19 May 2016 09:15

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