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T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria

T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria
T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria
Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-γ induction in response to non-cognate stimulation, while IL-15R expression was dispensable. Interestingly, effector Th1 cells generated by immunization rather than live infection had lower non-cognate activity despite comparable IL-18R and DR3 expression. Mice lacking T cell intrinsic expression of MyD88, an important adapter molecule in non-cognate T cell stimulation, exhibited higher bacterial burdens upon infection with Salmonella, Chlamydia or Brucella, suggesting that non-cognate Th1 stimulation is a critical element of efficient bacterial clearance. Thus, IL-18R and DR3 are critical players in non-cognate stimulation of Th1 cells and this response plays an important role in protection against intracellular bacteria.
1553-7366
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Pham, Oanh
eeb00437-4576-4aa3-84f4-87bba7e7e2dd
O'Donnell, Hope
d45f7152-7712-4128-9cea-3e8394377817
Kerrinnes, Tobias
fb6d8009-ec5f-4687-b80c-6ce02042467a
Tsolis, Renne
78287ce9-f8c3-4031-8b05-11c51bff4d72
McSorley, Stephen
5315e93c-0e8a-4738-8c58-c6dac77046a3
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Pham, Oanh
eeb00437-4576-4aa3-84f4-87bba7e7e2dd
O'Donnell, Hope
d45f7152-7712-4128-9cea-3e8394377817
Kerrinnes, Tobias
fb6d8009-ec5f-4687-b80c-6ce02042467a
Tsolis, Renne
78287ce9-f8c3-4031-8b05-11c51bff4d72
McSorley, Stephen
5315e93c-0e8a-4738-8c58-c6dac77046a3

Al-Shamkhani, Aymen, Pham, Oanh, O'Donnell, Hope, Kerrinnes, Tobias, Tsolis, Renne and McSorley, Stephen (2017) T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria PLoS Pathogens (doi:10.1371/journal.ppat.1006566).

Record type: Article

Abstract

Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-γ induction in response to non-cognate stimulation, while IL-15R expression was dispensable. Interestingly, effector Th1 cells generated by immunization rather than live infection had lower non-cognate activity despite comparable IL-18R and DR3 expression. Mice lacking T cell intrinsic expression of MyD88, an important adapter molecule in non-cognate T cell stimulation, exhibited higher bacterial burdens upon infection with Salmonella, Chlamydia or Brucella, suggesting that non-cognate Th1 stimulation is a critical element of efficient bacterial clearance. Thus, IL-18R and DR3 are critical players in non-cognate stimulation of Th1 cells and this response plays an important role in protection against intracellular bacteria.

Text journal.ppat.1006566 - Version of Record
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Accepted/In Press date: 1 August 2017
e-pub ahead of print date: 17 August 2017

Identifiers

Local EPrints ID: 414804
URI: http://eprints.soton.ac.uk/id/eprint/414804
ISSN: 1553-7366
PURE UUID: d8f69883-8541-4ecc-a9e2-1676b45995bd

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Date deposited: 11 Oct 2017 16:31
Last modified: 01 Nov 2017 17:30

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Contributors

Author: Oanh Pham
Author: Hope O'Donnell
Author: Tobias Kerrinnes
Author: Renne Tsolis
Author: Stephen McSorley

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