Automatic protection from tuberculosis?

Question

Hello,

at the moment I am working on a homework assay about cystic fibrosis. When doing my research I came upon the following statements: "Until now science could not give any conclusive explanation why an allele, that causes such a severe disease, is quite frequently found in the population and does not disappear with time....

One explanation could be the possible link between the predisposition for cystic fibrosis and protection against tuberculosis." Source: Wikipedia. Here comes my question: How is the illness exactly connected to a protection against tuberculosis?

Answer

Hello, I have never heard about a connection between tuberculosis and cystic fibrosis. Therefore we asked Prof. Döring from Tübingen, he wrote:

In the Caucasian population the frequency of being heterozygous for CF is quite high (1/20) and therefore it may be possible that this reflects an advantage of being heterozygous in respect of infectious diseases. Indeed animal experiments revealed that mice being heterozygous for CF were relatively resistant to cholera toxin (Gabriel et al, 1994), infections with Salmonella typhi (Pier, 1998) and diarrhea caused by E. coli (Markert 1995). The connection to CF is based on the fact that the toxins from Vibrio cholerae and E. coli are causing dehydration of the epithelial cells in the bowel and the chloride channel CFTR is playing a role in the pathophysiology of this dehydration. In case of dysfunction of the CFTR the degree of dehydration is much less in heterozygous individuals. Concerning infection with Salmonella typhi it is supposed that S. typhi needs the CFTR to get into the epithelial cells of the bowel. In case of dysfunction those bacteria cannot reach the inside of the epithelial cell. Until now these results have not been confirmed by investigations from other working groups or probably in other animal models.

References:

1. Gabriel SE. Brigman KN. Koller BH. Boucher RC. Stutts MJ. Cystic fibrosis heterozy-gote resistance to cholera toxin in the cystic fibrosis mouse model Science. 266:107-9, 1994

2. Pier GB. Grout M. Zaidi T. Meluleni G. Mueschenborn SS. Banting G. Ratcliff R. Evans MJ. Colledge WH. Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature. 393:79-82, 1998

3. Markert T. Vaandrager AB. Gambaryan S. Pohler D. Hausler C. Walter U. De Jonge HR. Jarchau T. Lohmann SM. Endogenous expression of type II cGMP-dependent protein ki-nase mRNA and protein in rat intestine. Implications for cystic fibrosis transmembrane conductance regulator. J Clin Invest. 96:822-30, 1995



I hope this answer is covering your question.

Yours sincerely,

Prof. Dr. TOF Wagner

31.10.2007