Toll‐like receptor 1 and 10 variations increase asthma risk and review highlights further research directions

Abstract

Aim: This paper summarises variations in the genes encoding toll-like receptors (TLRs) in relation to the aetiology and outcome of infant bronchiolitis. It compares the literature with research carried out by our group. infants were hospitalised for bronchiolitis and then followed up: 129 at 1.5 years of age, 166 at 5-7 years of age and 138 at 11-13 years of age.Results: The review showed that the Finnish bronchiolitis study was the only prospective study on the association between TLRs and the emergence of childhood asthma or lung function reduction after bronchiolitis in infancy. It found that TLR1 and TLR10 variant genotypes were associated with more asthma at 5-7 and 11-13 years, with inconsistent results for the other eight TLR genes. Large population-based studies were also identified that stressed the importance of the TLR2 subfamily members in childhood asthma. Conclusion:Our study found that variations in the TLR1 and TLR10 genes increased the asthma risk after bronchiolitis. The mini review calls for further research on the TLR2 subfamily in bronchiolitis and childhood asthma. 1406

Interleukin‐1 receptor‐associated kinase‐4 gene variation may increase post‐bronchiolitis asthma risk

“…We have collected prospective follow‐up data at two control visits at 5‐7 years 9 and 11‐13 years 10 of ages from children hospitalised for bronchiolitis under 6 months of age. As summarised previously, 11 TLR5 variation was associated with virus aetiology of bronchiolitis, TLR9 variation with post‐bronchiolitis wheezing, and TLR1 and TLR10 variations with post‐bronchiolitis asthma at school age.…”

“…We included the IRAK4 rs4251513 and rs4251520 in our study based on previous findings made in two European birth cohorts 8 . The rationale for studying IRAK4 polymorphisms in this post‐bronchiolitis cohort came from our observations on the role of TLR polymorphisms in bronchiolitis and post‐bronchiolitis outcome 11 . IRAK4 plays a crucial role in innate immunity mediating signals initiated by TLRs after recognising of pathogens, which are mediated to IRAK4 and other transduction molecules via TIR domains which consists of TLRs and IL‐1 receptors 1,2 …”

Toll-like receptor 3 -926T>A increased the risk of breast cancer through decreased transcriptional activity

“…For example, TLR1 recognizes various bacterial components and initiates complex downstream NF-κB and MAPK pathways. [13][14][15] TLRs may lead to immune tolerance and cancer progression. 2 Some TLR agonists have been studied in tumor therapy in attempts to change immune tolerance into antitumor immunity.…”

Genetic variations in Toll‐like receptors 4 or 7 were not linked to post‐bronchiolitis lung function in adolescence

“…Our original post‐bronchiolitis cohort comprised 166 children, hospitalised for bronchiolitis at less than six months of age and followed until 5‐7 years of age 3 . At 10‐13 years of age, 89 of them underwent flow‐volume spirometry (Vmax Carefusion, Becton, Dickinson and Company, Franklin Lakes, NJ, USA) before and after bronchodilation 2 .…”

“…We have prospectively followed the post‐bronchiolitis cohort enrolled in 2001‐2004 in Tampere, Finland, and we recently reported that single nucleotide polymorphism (SNP) of the TLR10 rs4129009 was associated with better lung function in 81 children at 10‐13 years of age 2 . This SNP was also associated with asthma at 5‐7 years of age and with persistent asthma from that age to 10‐13 years 3 . The genes encoding TLR1, TLR2 and TLR6, the other three members of the TLR2 subfamily, showed no association with lung function in adolescence 2 …”