Ling, Guang Sheng, Bennett, Jason, Woollard, Kevin J., Szajna, Marta, Fossati-Jimack, Liliane, Taylor, Philip R.  ORCID: https://orcid.org/0000-0003-0163-1421, Scott, Diane, Franzoso, Guido, Cook, H. Terence and Botto, Marina
2014.
Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages.
Nature Communications
5
, 3039.
10.1038/ncomms4039
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Abstract
Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin αM (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| Date of First Compliant Deposit: | 30 March 2016 |
| Date of Acceptance: | 2 December 2013 |
| Last Modified: | 05 May 2023 23:32 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/79450 |
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