6 Escherichia coli Heat-Labile Enterotoxin (LTS61K) Modulates Dendritic Cell Function and Attenuates Airway Inflammation in Mouse Model of Allergic Asthma

BACKGROUND: Escherichia coli heat-labile enterotoxin (LT) with different mutant forms has been used as adjuvant for vaccines due to its ability to enhance immune response to specific antigen in vivo. We hypothesis that LTS61K or LTS61K mixed with dust mite allergen, Der p, (LTS61K/Der p) can modulate dendritic cells (DCs) s' functions thus alleviate allergen-induced airway inflammation. METHODS: Two protocols (ie, preventive and therapeutic protocol) were designed to evaluate the effects of LTS61K in Der p sensitized and challenged mouse model of asthma. RESULTS: Both intranasal inoculations with LTS61K or LTS61K/Der p decreased allergen-induced airway inflammation and alleviated systemic T(H)2-type immune response. In addition, bronchoalveolar lavage (BAL) fluids and sera from LTS61K/Der p treated mice have higher concentrations of Der p-specific IgA than those of other groups. In the in vitro study, bone marrow-derived dendritic cells (BMDCs) and DC cell line, DC2.4 cells stimulated with LTS61K/Der p both secreted pro-inflammation cytokines IL-6 and TNF-a. In contrast, after LTS61K treatment, only BMDCs decreased production of IL-6 and TNF-a as well as decreased maturation. Furthermore, we found that pre-treatment BMDC with LTS61K inhibited Der p-induced NF-kB translocation which might explain the delayed maturation and decreased productions of IL-6 and TNF-a in LTS61K pre-treated BMDCs. Intratracheally adoptive transferred with LTS61K- or LTS61K/Der p-primed DC2.4 cells or BMDCS into Der p-sensitized mice decreased inflammatory cells infiltration and T(H)2-type chemokines in BAL fluids and alleviated airway inflammation. CONCLUSIONS: Our results show that LTS61K may influence DCs maturation and its cytokine production. On the other hands, LTS61K/Der p may induce more Der p-specific IgA production to decrease allergic T(H)2 cytokine responses and alleviate airway inflammation in murine model of asthma. These finding suggested that LTS61K may have clinical application as an immune-modulator effect on the diseases of allergy and asthma.