A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen

Abstract

It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoides farinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-gamma released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases.

Fig. 1

Total cell and eosinophil counts in BALF decreased significantly after Pam3CSK4 treatment Pam3CSK4 was given to allergic mice once 1 d before the last intranasal challenge. ^** P<0.001, as compared with PBS mice; ^∆ P<0.01, as compared with untreated Der f-allergic mice

Fig. 2

Pam3CSK4 enhanced IFN-γ and inhibited IL-13 productions. (a) IFN-γ in BALF; (b) IL-13 in BALF; (c) IFN-γ released from splenocytes stimulated with Der f; (d) IL-13 released from splenocytes stimulated with Der f ^** P<0.001 and ^* P<0.01, as compared with untreated Der f-allergic rhinitis mice. ND: Not detected

Fig. 2

Pam3CSK4 enhanced IFN-γ and inhibited IL-13 productions. (a) IFN-γ in BALF; (b) IL-13 in BALF; (c) IFN-γ released from splenocytes stimulated with Der f; (d) IL-13 released from splenocytes stimulated with Der f ^** P<0.001 and ^* P<0.01, as compared with untreated Der f-allergic rhinitis mice. ND: Not detected

Fig. 2

Pam3CSK4 enhanced IFN-γ and inhibited IL-13 productions. (a) IFN-γ in BALF; (b) IL-13 in BALF; (c) IFN-γ released from splenocytes stimulated with Der f; (d) IL-13 released from splenocytes stimulated with Der f ^** P<0.001 and ^* P<0.01, as compared with untreated Der f-allergic rhinitis mice. ND: Not detected

Fig. 2

Pam3CSK4 enhanced IFN-γ and inhibited IL-13 productions. (a) IFN-γ in BALF; (b) IL-13 in BALF; (c) IFN-γ released from splenocytes stimulated with Der f; (d) IL-13 released from splenocytes stimulated with Der f ^** P<0.001 and ^* P<0.01, as compared with untreated Der f-allergic rhinitis mice. ND: Not detected

Fig. 3

The total serum IgE decreased remarkably after Pam3CSK4 treatment ^** P<0.001, as compared with PBS mice; ^∆ P<0.05, as compared with untreated Der f-allergic rhinitis mice