Gambiense Human African Trypanosomiasis and Immunological Memory: Effect on Phenotypic Lymphocyte Profiles and Humoral Immunity

Abstract

In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and that B-cell dysfunction might not be that severe as in mouse models.

Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells

“…b . gambiense show a significant increase in T cell-independent B cells and a significant decrease in T cell-dependent B cells as a percentage of total blood lymphocytes accompanied by a significant decrease in anti-measles antibody in serum relative to age-, gender- and habitat-matched uninfected individuals, although not of a level to compromise immunity [ 28 ]. It remains possible that there is a link between the infection-induced mechanism that causes the depletion of splenic B2 B cells in trypanosome-infected mice, and those that prevent the development of trypanosome-specific IgG antibodies in infected cattle [ 29 ] and cause the proportional decrease in T cell-dependent relative to T cell-independent B cells in the peripheral blood of T .…”

Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity

“…African sleeping sickness is a vector borne disease of mammals, caused by Trypanosoma brucei ( T. brucei ), for which the development of more effective, safe, and affordable chemotherapies remains a major goal. Vaccines are unlikely to be suitable [1] – [3] , and therefore disease control relies exclusively on chemotherapy. The glucose-based metabolism is a key metabolic pathway for bloodstream forms, the mammalian infective stages.…”

Curative drug treatment of trypanosomosis leads to the restoration of B‐cell lymphopoiesis and splenic B‐cell compartments

“…Of note, Lejon et al . recently reported a reduction in memory B cells in HAT patients, although after curative treatment, antimeasles antibodies recovered to a critical threshold level. However, the protective capacity of the recovered response could not be assessed, and the authors suggested themselves that it would be crucial to assess antibody functionality in the future.…”