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The TLR4–TRIF pathway can protect against the development of experimental allergic asthma
Author(s) -
Shalaby Karim H.,
Al Heialy Saba,
Tsuchiya Kimitake,
Farahnak Soroor,
McGovern Toby K.,
Risse PaulAndre,
Suh WoongKyung,
Qureshi Salman T.,
Martin James G.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12755
Subject(s) - trif , medicine , immunology , tlr2 , nasal administration , toll like receptor , signal transducing adaptor protein , immune system , innate immune system , receptor
Summary 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 TLR 4‐dependent inhibition of allergic airway disease and induction of CD 4 + ICOS + T cells by nasal application of Protollin™, a mucosal adjuvant composed of TLR 2 and TLR4 agonists. Wild‐type (WT), Trif −/− or Myd88 −/− mice were sensitized to birch pollen extract ( BPE x), then received intranasal Protollin followed by consecutive BPE x challenges. Protollin's protection against allergic airway disease was TRIF ‐dependent and MyD88‐independent. TRIF deficiency diminished the CD 4 + 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 CD 4 + ICOS + Foxp3 − cells, in particular. Adoptive transfer of cervical lymph node cells supported a role for Protollin‐induced CD 4 + ICOS + cells in the TRIF ‐dependent inhibition of airway hyper‐responsiveness. Hence, our data demonstrate that stimulation of the TLR 4‐ TRIF pathway can protect against the development of allergic airway disease and that a TRIF ‐dependent adjuvant effect on CD 4 + ICOS + T‐cell responses may be a contributing mechanism.