Local treatment with BPPcysMPEG reduces allergic airway inflammation in sensitized mice.
According to the hygiene hypothesis, triggering the immune system with microbial components during childhood balances the inherent Th2 bias. In contrast, specific immunotherapy involves exposure of the patient to the allergen in order to achieve desensitization to subsequent contact. In a human in vitro allergy model the potential of the TLR2/6 agonist BPPcysMPEG to modulate antigen presenting cells and allergen-specific immune responses was evaluated. Specific immunomodulation via co-administration of the allergen and BPPcysMPEG enhanced expression of co-stimulatory molecules on DC and increased secretion of the proinflammatory cytokine TNF-α. Acting as an adjuvant, BPPcysMPEG elevated allergen-specific immune responses in co-culture with autologous lymphocytes. Although administration of BPPcysMPEG alone enhanced expression of co-stimulatory molecules on DC, proliferation of autologous lymphocytes was not induced. Based on this finding, the potential of BPPcysMPEG to reduce allergic airway inflammation by preventive modulation of the innate immune system via TLR2/6 agonization was investigated in mice. Local administration of BPPcysMPEG altered cellular influx and cell composition in BAL fluid. Furthermore, the Th2-associated cytokines IL-4 and IL-5 were diminished. Allergen-specific restimulation of cells from mediastinal lymph nodes and splenocytes suggested an alteration of immune responses. The treatment with BPPcysMPEG induced a Th1-dominated cytokine milieu in mediastinal lymph nodes, while allergen-specific immune responses in splenocytes were diminished. The co-administration of allergen and BPPcysMPEG reduced cytokine secretion upon restimulation in mediastinal lymph nodes and splenocytes. From these data we conclude that BPPcysMPEG was able to influence the immune system with regard to subsequent allergen contact by TLR2/6 agonization.
Knothe
S
S
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department of Immunology, Allergology and Immunotoxicology, Hannover, Germany.
Mutschler
V
V
Rochlitzer
S
S
Winkler
C
C
Ebensen
T
T
Guzman
C A
CA
Hohlfeld
J
J
Braun
A
A
Muller
M
M
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D055666:Lipopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000494:pharmacology; D020239:Receptor Cross-Talk; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000819:agonists; D051216:Toll-Like Receptor 6 / Q000819:agonists
D000485:Allergens; D016207:Cytokines; D055666:Lipopeptides; C549816:S-(2,3-bispalmitoyloxypropyl)-cysteinyl-amido-monomethoxyl polyethylene glycol; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D011092:Polyethylene Glycols