Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages

Guang Sheng Ling, Jason Bennett, Kevin J. Woollard, Marta Szajna, Liliane Fossati-Jimack, Philip R. Taylor, Diane Scott, Guido Franzoso, H. Terence Cook, H. Terence Cook

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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.
Original languageEnglish
Article number3039
Number of pages12
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 15 Jan 2014
Externally publishedYes

Bibliographical note

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.

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