Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by trypanolytic factor 1

Background: the three sub-species of trypanosoma brucei are important pathogens of sub-saharan africa. t. b. brucei is unable to infect humans due to sensitivity to trypanosome lytic factors (tlf) 1 and 2 found in human serum. t. b. rhodesiense and t. b. gambiense are able to resist lysis by tlf. there are two distinct sub-groups of t. b. gambiense that differ genetically and by human serum resistance phenotypes. group 1 t. b. gambiense have an invariant phenotype whereas group 2 show variable resistance. previous data indicated that group 1 t. b. gambiense are resistant to tlf-1 due in-part to reduced uptake of tlf-1 mediated by reduced expression of the tlf-1 receptor (the haptoglobin-hemoglobin receptor (hphbr)) gene. here we investigate if this is also true in group 2 parasites. methodology: isogenic resistant and sensitive group 2 t. b. gambiense were derived and compared to other t. brucei parasites. both resistant and sensitive lines express the hphbr gene at similar levels and internalized fluorescently labeled tlf-1 similar fashion to t. b. brucei. both resistant and sensitive group 2,as well as group 1 t. b. gambiense,internalize recombinant apol1,but only sensitive group 2 parasites are lysed. conclusions: our data indicate that,despite group 1 t. b. gambiense avoiding tlf-1,it is resistant to the main lytic component,apol1. similarly group 2 t. b. gambiense is innately resistant to apol1,which could be based on the same mechanism. however,group 2 t. b. gambiense variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of hphbr. thus there are differences in the mechanism of human serum resistance between t. b. gambiense groups 1 and 2. © 2011 capewell et al.