TRIF Deficiency does not Affect Severity of Ovalbumin-induced Airway Inflammation in Mice

Abstract

Allergic asthma is a chronic pulmonary inflammatory disease characterized by reversible airway obstruction, hyperresponsiveness and eosinophils infiltration. Toll-like receptors (TLRs) signaling are closely associated with asthma and have emerged as a novel therapeutic target in allergic disease. The functions of TLR3 and TLR4 in allergic airway inflammation have been studied; however, the precise role of TIR-domain-containing adapter-inducing interferon-β (TRIF), the adaptor molecule for both TLR3 and TLR4, is not yet fully understood. To investigate this, we developed a mouse model of OVA-induced allergic airway inflammation and compared the severity of allergic airway inflammation in WT and TRIF(-/-) mice. Histopathological assessment revealed that the severity of inflammation in airway inflammation in TRIF-deficient mice was comparable to that in WT mice. The total number of cells recovered from bronchoalveolar lavage fluid did not differ between WT and TRIF-deficient mice. Moreover, TRIF deficiency did not affect Th1 and Th2 cytokine production in lung tissue nor the level of serum OVA-specific IgE, IgG1 and IgG2c. These findings suggest that TRIF-mediated signaling may not be critical for the development of allergic airway inflammation.

Keywords: Allergic airway inflammation; TRIF; Th2.

Figure 1

A schematic diagram of the experimental design of an OVA-induced model of allergic airway inflammation. Sensitization of OVA was performed at day 0 (D0) and day 7 (D7) by intraperitoneal (i.p.) injection of OVA with aluminum hydroxide used as an adjuvant. From days 14 to 16, mice were inranasally (i.n.) challenged with OVA and were sacrificed 2 days after last challenge.

Figure 2

Airway inflammation of TRIF^-/- mice was comparable to that observed in WT mice. (A) In microscopic analysis of hematoxylin and eosin (H&E)-stained tissue sections, inflammatory cells infiltrating around the bronchus and the alveolar interstitium of OVA sensitized-challenged WT and TRIF^-/- mice were observed. (B) No significant difference in severity score was observed between OVA-treated WT and TRIF^-/- lung tissue. (C) The total number of cells in bronchoalveolar lavage (BAL) fluid was increased in OVA-treated mice; however, the mean number was similar in OVA-treated WT and TRIF^-/- mice. Data are shown as mean±SD of each group (n=5 per group).

Figure 3

The production of Th1 and Th2 cytokine in the lung extract was not influenced by TRIF-deficiency. The levels of the type 2 cytokines_IL-5 (A) and IL-13 (B) were increased in OVA-treated mice compared with PBS treated control mice. However, no difference was observed between WT and TRIF^-/- mice. The level of the type 1 cytokine_IL-12 (C) was also increased in OVA-treated mice but did not significantly differ between in WT and TRIF^-/- mice. (D) IFN-γ secretion was not affected by OVA treatment in WT and TRIF^-/- mice. Data are shown as mean±SD of each group (n=5 per group).

Figure 4

The level of OVA-specific IgG₁ was decreased in TRIF^-/- mice. The OVA-specific antibody subclasses (A) IgE, (B) IgG₁, and (C) IgG_2c were increased in OVA-treated mice. No significant difference in IgE, IgG₁, and IgG_2c levels was observed in OVA-treated WT and TRIF^-/- mice. Data are shown as mean±SD of each group (n=5 per group).