Different toll-like receptors (TLRs) and nod-like receptors (NLRs) expression profiles in lung tissue during mild and severe experimental asthma

RATIONALE: Inflammatory disorders, such as asthma, are caused by aberrant immune regulation in which various signaling receptors are involved. Pathogen recognition receptors like the TLRs and NLRs families of receptors are one of the key components of the innate immune system. The function of these receptors has been linked to susceptibility towards the development of allergic diseases, including asthma, making the TLRs and NLRs potential targets for novel therapies against allergic diseases. Patients show different disease severity, including mild and severe asthma. Asthma treatment based on disease subphenotypes might improve asthma management. METHODS: In this study the mRNA expression levels of TLRs and NLRs in lung tissue in a mild and severe mouse models of allergic asthma were measured. In the mild model the mice were sensitized with ovalbumin (OVA)-imject alum and challenged with OVA. In the severe model the mice were sensitized with trinitrophenyl-ovalbumin (TNP-OVA) and challenged with TNP-OVA-IgE. To investigate the mRNA expression levels of the different TLRs in whole lung tissue, quantitative real-time polymerase chain reaction (q-PCR) was used. The expression of TLR1toTLR13 and two NLR (NOD-1 and NOD-2) receptors was studied. In addition, broncho-alveolar lavage fluid (BALF) was collected and cell numbers analyzed. RESULTS: In the mild model, challenge with ovalbumin increased the mRNA expression of TLR9, 11 and 12. In the severe model challenge with trinitrophenyl-ovalbumin-IgE increased the expression of TLR1, 2, 4, 7, 8 and 9 and decreased the expression of TLR3. Compared to the total cell number in BALF in the mild model, a higher total cell number is seen in the sever model. In addition, in the severe asthma model, a higher cell influx of eosinophils in BALF is shown compared to the cell influx in the mild model. A significant inverse correlation is found between the mRNA expression of TLR3 and the total cell number in BALF. The expression of TLR6 and TLR9 showed a significant direct correlation with the total cell number in BALF. CONCLUSIONS: In the mild and severe asthma models different TLRs and NLRs expression profiles were obsorved. In the severe asthma model, a higher level of cell influx in BALF was seen compared to the mild model. A significant correlation is found between the mRNA expression of TLR3, TLR6 and TLR9 and the total cell number in BALF. Different therapies might be needed for the management of mild and severe asthma.