The TLR4-TRIF pathway can protect against the development of experimental allergic asthma.

Autor: Shalaby KH; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., Al Heialy S; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., Tsuchiya K; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., Farahnak S; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., McGovern TK; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., Risse PA; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., Suh WK; Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada., Qureshi ST; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada., Martin JG; Department of Medicine, Meakins-Christie Laboratories, McGill University Health Centre Research Institute, McGill University, Montréal, QC, Canada.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2017 Sep; Vol. 152 (1), pp. 138-149. Date of Electronic Publication: 2017 Jun 20.
DOI: 10.1111/imm.12755
Abstrakt: The Toll-like receptor (TLR) adaptor proteins myeloid differentiating factor 88 (MyD88) and Toll, interleukin-1 receptor and resistance protein (TIR) domain-containing adaptor inducing interferon-β (TRIF) comprise the two principal limbs of the TLR signalling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4 + ICOS + T cells by nasal application of Protollin™, a mucosal adjuvant composed of TLR2 and TLR4 agonists. Wild-type (WT), Trif -/- or Myd88 -/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges. Protollin's protection against allergic airway disease was TRIF-dependent and MyD88-independent. TRIF deficiency diminished the CD4 + ICOS + T-cell subsets in the lymph nodes draining the nasal mucosa, as well as their recruitment to the lungs. Overall, TRIF deficiency reduced the proportion of cervical lymph node and lung CD4 + ICOS + Foxp3 - cells, in particular. Adoptive transfer of cervical lymph node cells supported a role for Protollin-induced CD4 + ICOS + cells in the TRIF-dependent inhibition of airway hyper-responsiveness. Hence, our data demonstrate that stimulation of the TLR4-TRIF pathway can protect against the development of allergic airway disease and that a TRIF-dependent adjuvant effect on CD4 + ICOS + T-cell responses may be a contributing mechanism.
(© 2017 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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