Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects.
J Allergy Clin Immunol
; 139(2): 667-678.e5, 2017 02.
Article
in En
| MEDLINE
| ID: mdl-27544739
ABSTRACT
BACKGROUND:
Bacterial cowshed isolates are allergy protective in mice; however, the underlying mechanisms are largely unknown. We examined the ability of Lactococcus lactis G121 to prevent allergic inflammatory reactions.OBJECTIVE:
We sought to identify the ligands and pattern recognition receptors through which L lactis G121 confers allergy protection.METHODS:
L lactis G121-induced cytokine release and surface expression of costimulatory molecules by untreated or inhibitor-treated (bafilomycin and cytochalasin D) human monocyte-derived dendritic cells (moDCs), bone marrow-derived mouse dendritic cells (BMDCs), and moDC/naive CD4+ T-cell cocultures were analyzed by using ELISA and flow cytometry. The pathology of ovalbumin-induced acute allergic airway inflammation after adoptive transfer of BMDCs was examined by means of microscopy.RESULTS:
L lactis G121-treated murine BMDCs and human moDCs released TH1-polarizing cytokines and induced TH1 T cells. Inhibiting phagocytosis and endosomal acidification in BMDCs or moDCs impaired the release of TH1-polarizing cytokines, costimulatory molecule expression, and T-cell activation on L lactis G121 challenge. In vivo allergy protection mediated by L lactis G121 was dependent on endosomal acidification in dendritic cells (DCs). Toll-like receptor (Tlr) 13-/- BMDCs showed a weak response to L lactis G121 and were unresponsive to its RNA. The TH1-polarizing activity of L lactis G121-treated human DCs was blocked by TLR8-specific inhibitors, mediated by L lactis G121 RNA, and synergistically enhanced by activation of nucleotide-binding oligomerization domain-containing protein (NOD) 2.CONCLUSION:
Bacterial RNA is the main driver of L lactis G121-mediated protection against experimentally induced allergy and requires both bacterial uptake by DCs and endosomal acidification. In mice L lactis G121 RNA signals through TLR13; however, the most likely intracellular receptor in human subjects is TLR8.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endosomes
/
Dendritic Cells
/
RNA, Bacterial
/
Milk Hypersensitivity
/
Lactococcus lactis
/
Lung
/
Antigens, Bacterial
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2017
Document type:
Article
Affiliation country: