Cystic fibrosis CFBE41o- cells contain TLR1 SNP I602S and fail to respond to Mycobacterium abscessus.

BACKGROUND: Mycobacterium abscessus causes lung infection in patients with cystic fibrosis. M. abscessus stimulates the host innate immune response via TLR2 on respiratory epithelial cells. Signaling through TLR2 requires the formation of TLR2/TLR1 heterodimers on the cell surface.
METHODS: The ability of M. abscessus to stimulate the innate immune response of cystic fibrosis CFBE41o- respiratory epithelial cells was measured as expression of HβD2 by RT PCR, and release of IL-8 by ELISA. Genotyping of CFBE41o- TLR polymorphisms was carried out.
RESULTS: CFBE41o- cells are hyporesponsive to M. abscessus. They are homozygous for the TLR1 SNP I602S which has been demonstrated to cause diminished cellular responses to TLR2 agonists.
CONCLUSIONS: Homozygosity for I602S is prevalent in Western Europeans and North American Caucasians, the same demographic in which the ΔF508 mutation is present. This SNP may play a role in the pathogenesis of M. abscessus lung infection in patients with cystic fibrosis. Published by Elsevier B.V.