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

  • Researchers

    Kempaiah P, Davidson LB, Perkins DJ, Byrd TF.

  • Place of research

    The University of New Mexico School of Medicine, New Mexico, USA.

  • Publication

    Journal of Cystic Fibrosis / December 2013

  • Subjects

    , , ,

  • Do genetic factors predispose people with CF to develop Mycobacterium abscessus lung infection?

  • Why is this important?

    Mycobacterium absessus (a form of non-tuberculous mycobacteria (NTM)) can cause infection in CF and is often difficult to treat. If it was possible to identify patients at greatest risk, an antibiotic could be given at low dose that could prevent the bacteria from gaining a foothold in the lung.

  • What did you do?

    We studied a type of cell obtained from the lung airways of a patient with CF. This cell has been immortalized using laboratory techniques, and is designated the CFBE41o‐ cell line.

  • What did you find?

    Receptors on cell surfaces are analogous to antennae, sensing what is in the local environment. Toll-like receptors (TLRs) are linked at the cell surface and recognize NTM. We found that CFBE41o‐ cells do not respond to M. abscessus due to a variation in the gene. This variation is called I602S and renders TLR1 nonfunctional. It is very common in Caucasians of northern European ancestry, the same population in which the CF ΔF508 is common, and it influences susceptibility to infection with other mycobacteria.

  • What does this mean and reasons for caution?

    Possessing this gene variation may influence the susceptibility of people with CF to lung infection with M. abscessus. Whilst we have seen this in the lab it is not yet known whether this causes infection in patients.

  • What's next?

    A clinical study to determine the influence of this variation on susceptibility of CF patients to chronic NTM lung infection is needed. Those with NTM lung infection can be assessed for the presence of this gene variation and compared to CF patients with chronic lung infection caused by other types of bacteria.