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Journal articles
TLR1/2 orchestrate human plasmacytoid predendritic cell response to gram+ bacteria
Abstract : Gram+ infections are worldwide life-threatening diseases in which the pathological role of type I interferon (IFN) has been highlighted. Plasmacytoid predendritic cells (pDCs) produce high amounts of type I IFN following viral sensing. Despite studies suggesting that pDCs respond to bacteria, the mechanisms underlying bacterial sensing in pDCs are unknown. We show here that human primary pDCs express toll-like receptor 1 (TLR1) and 2 (TLR2) and respond to bacterial lipoproteins. We demonstrated that pDCs differentially respond to gram+ bacteria through the TLR1/2 pathway. Notably, up-regulation of costimulatory molecules and pro-inflammatory cytokines was TLR1 dependent, whereas type I IFN secretion was TLR2 dependent. Mechanistically, we demonstrated that these differences relied on diverse signaling pathways activated by TLR1/2. MAPK and NF-κB pathways were engaged by TLR1, whereas the Phosphoinositide 3-kinase (PI3K) pathway was activated by TLR2. This dichotomy was reflected in a different role of TLR2 and TLR1 in pDC priming of naïve cluster of differentiation 4+ (CD4+) T cells, and T helper (Th) cell differentiation. This work provides the rationale to explore and target pDCs in bacterial infection.
Cited literature [45 references]
https://www.hal.inserm.fr/inserm-02137403
Contributor : Myriam Bodescot Connect in order to contact the contributor
Submitted on : Thursday, May 23, 2019 - 8:48:33 AM
Last modification on : Wednesday, October 20, 2021 - 12:20:53 AM
Contributor : Myriam Bodescot Connect in order to contact the contributor
Submitted on : Thursday, May 23, 2019 - 8:48:33 AM
Last modification on : Wednesday, October 20, 2021 - 12:20:53 AM
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journal.pbio.3000209.pdf
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