Normal Human Serum Lysis of Non-human Trypanosomes and Resistance of T. b. rhodesiense and T. b. gambiense

Abstract

Trypanosoma brucei can be segregated into three morphologically identical sub-species based on host, geography and pathology. T. b. brucei is limited to domestic and wild animals throughout sub-Saharan Africa and is non-infective to humans due to trypanosome lytic factors found in human serum. There are two trypanosome lytic factors in human serum (TLF-1 & 2), both containing the proteins Apolipoprotein L1 (APOL1) and Haptoglobin-related protein (HPR). It has been conclusively demonstrated that the lytic component of TLF is APOL1, although HPR is required for maximal lysis by facilitating uptake of TLF particles via the HpHbR cell surface receptor. T. b. gambiense and T. b. rhodesiense are able to resist these lytic factors to cause human African sleeping sickness. T. b. rhodesiense is able to neutralise APOL1 due to expression of Serum Resistance-Associated gene (SRA). SRA is not found in the more prevalent human infective sub-species, T. b. gambiense, which causes over 97 % of reported human cases. Study of T. b. gambiense is complicated in that there are two distinct groups. Group 1 is invariably resistant to lysis and by far the more prevalent group. Group 2 T. b. gambiense exhibit a variable resistance phenotype and are only found at a small number of Cote d’Ivoire and Burkina Faso foci. Little is known as to how both groups are able to resist lysis by normal human serum; however, members of group 1 T. b. gambiense display both reduced expression and activity of HpHbR that may contribute to the resistance phenotype.