Thus far we have reviewed the influence of the specificity of vectors, as well as the habitat and age of the hosts, and even the season of the year on the infection capabilities and density of infection of different species of Trypanosoma. Today we will delve even deeper into the stores of knowledge on trypanosomes. More specifically, we will learn how the length of the telomeres on the end of the genes in Trypanosoma brucei can affect the frequency of antigenic variation, which is the parasite's main means of avoiding its hosts immune system (Galadriel et al., 2012).
First, let us recap. Recall from our Parasitology class that one way for the immune system to recognize a pathogen is by the antigens present on the surface of the invading cell. Trypanosomes are capable of evading the defenses of a host by varying the antigens present on the surface of the parasite. This antigenic variation can be coded for by any one of approximately 1,000 Variant Surface Glycoprotein (VSG) genes within Trypanosoma brucei. Also recall from Bio 230 (Genetics) that telomeres protect a chromosome from deterioration by repeating sequences of nucleotides on the end of the chromosome. It is also important to keep in mind that telomeres become shorter over time due to cell division.
The authors had hypothesized that the length of telomeres would directly affect the frequency of VSG switching. The method of study was relatively simple: the correlation which the authors proposed was examined by comparing the frequency at which "wild-type" or T. brucei with long telomeres switched the expression of glycoproteins to the frequency at which T. brucei with shortened telomeres switched the expression of glycoproteins. Ultimately, it was concluded that the length of telomeres did indeed influence the rate at which VSGs switched.
Most notably I have realized that the above information can be translated to the cycle of infection. Keep in mind that while infected with T. brucei, there are approximately 3 or 4 Variable Antigen Types (VATs) present within the human body with one VAT being dominant over all the rest. These VATs cause infections to cycle between high density and low density which also means that symptoms cycle from very severe to moderate. It is therefore entirely possible for the cycle to occur at a faster rate if there are populations of T. brucei present in the body which possess shortened telomeres! Scary stuff to say the least.
Literature Cited
Hovel-Miner, G.A., C.E. Boothroyd, M. Mugnier, O. Dreesen, G.A.M. Cross, F.N. Papavasilou. 2012. Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei. PLOS Pathogens. 8(8): pp. 1-10.
I like how you used class material to help us better understand the complexity of the genetics involved in this article. I wonder if this switching of VSGs for avoiding host defense affects the detection of infection at all.
ReplyDelete