Aspergillus fumigatus regulates mite allergen-pulsed dendritic cells in the development of asthma

作者：Fukahori S; Matsuse H^*; Tsuchida T; Kawano T; Tomari S; Fukushima C; Kohno S

来源：Clinical and Experimental Allergy, 2010, 40(10): 1507-1515.

DOI：10.1111/j.1365-2222.2010.03520.x

• allergy
• dendritic cells
• fungal
• lung
• tolerance

Background The role in allergic asthma development of the immune response against fungi with concomitant exposure to other common aeroallergens has yet to be determined. In particular, there is little understanding of how inhaled fungi affect the host response to mite allergens.
Objective To characterize the in vitro and in vivo effects of concurrent exposure of Aspergillus fumigatus (Af) and Dermatophagoides farinae (Derf) on dendritic cells (DCs) in the development of allergic asthma.
Methods Murine bone marrow-derived DCs were pulsed with Derf and/or live or heat-inactivated Af. Cytokine production and the expression of pathogen recognition receptors (PRRs) were determined in vitro. Subsequently, these DCs were inoculated into the airway of naive mice to assess the development of allergic airway inflammation in vivo. The effect of antibodies against PRRs was also evaluated.
Results Live Af significantly enhanced IL-10 production and the expression of Toll-like receptor (TLR) 2 and Dectin-1 in Derf-pulsed DCs. Live Af infection significantly attenuated Derf-pulsed DC-induced allergic airway inflammation in vivo. Antibodies against either TLR2 or Dectin-1 significantly reversed the inhibitory effects of live Af in the development of Derf-pulsed DC-induced allergic airway inflammation.
Conclusion Concurrent exposure of DCs to fungal antigens has profound influences on the subsequent mite allergen-induced allergic airway inflammation. Live Af could regulate the functions of airway DCs in the development of mite allergen-induced allergic airway inflammation via regulation of their PRRs.
Our results suggest that concurrent exposure to pathogens such as fungi and mite allergens has profound influences on the subsequent allergen-induced allergic airway inflammation. Furthermore, modulating PRR signalling could provide a therapeutic regimen for the development of asthma.

• 出版日期2010-10