Intrinsic immunosuppressive activity of different trypanosome strains varies with parasite virulence

Abstract

The virulence of African trypanosomes varies greatly with the host and parasite strain combinations used¹. In mice, infections range from those which are rapidly fatal to those which more closely resemble the chronic disease patterns seen in man and domestic cattle². The basis of trypanosome virulence is assumed to be related to intrinsic parasite replication rate and the effectiveness of the host's immune response to successive waves of parasites which differ in their surface antigens. Continued control of each emergent population requires sustained immune vigilance. Thus, the generalised immunodepression which accompanies African trypanosomiasis in man³, cattle⁴ and experimental animals^5,6 would be expected to determine the fatal outcome of most untreated infections if the secondary immunodeficiency extends to responses against the parasite as well as to unrelated antigens. Virulence, in this view, could be explained by the rapidity and intensity with which a given strain of trypanosomes induces immunodepression in a given host. We have attempted to define the relationship between parasite virulence and generalised immunodepression by examining the intrinsic potential of trypanosome strains of differing virulence to induce immunodepression in the same murine host. Following the observation that kiled trypanosomes or their subcellular membrane fractions mimic the immunological consequences of active infection in vivo⁷, it has now become possible to compare the immunosuppressive potential of acute and chronic strains by using active fractions derived from identical numbers of killed organisms. We conclude from these comparisons that trypanosome strains can have inherently different immunosuppressive activities, and that the extent to which IgM responses, in particular, are suppressed correlates with and suggests a basis for parasite virulence.