Role for Parasite Genetic Diversity in Differential Host Responses toTrypanosoma bruceiInfection

Abstract

The postgenomic era has revolutionized approaches to defining host-pathogen interactions and the investigation of the influence of genetic variation in either protagonist upon infection outcome. We analyzed pathology induced by infection with two genetically distinct Trypanosoma brucei strains and found that pathogenesis is partly strain specific, involving distinct host mechanisms. Infections of BALB/c mice with one strain (927) resulted in more severe anemia and greater erythropoietin production compared to infections with the second strain (247), which, contrastingly, produced greater splenomegaly and reticulocytosis. Plasma interleukin-10 (IL-10) and gamma interferon levels were significantly higher in strain 927-infected mice, whereas IL-12 was higher in strain 247-infected mice. To define mechanisms underlying these differences, expression microarray analysis of host genes in the spleen at day 10 postinfection was undertaken. Rank product analysis (RPA) showed that 40% of the significantly differentially expressed genes were specific to infection with one or the other trypanosome strain. RPA and pathway analysis identified LXR/RXR signaling, IL-10 signaling, and alternative macrophage activation as the most significantly differentially activated host processes. These data suggest that innate immune response modulation is a key determinant in trypanosome infections, the pattern of which can vary, dependent upon the trypanosome strain. This strongly suggests that a parasite genetic component is responsible for causing disease in the host. Our understanding of trypanosome infections is largely based on studies involving single parasite strains, and our results suggest that an integrated host-parasite approach is required for future studies on trypanosome pathogenesis. Furthermore, it is necessary to incorporate parasite variation into both experimental systems and models of pathogenesis.

Haematological Indices in Trypanosoma Brucei Brucei (Federe Isolate) Infected Nigerian Donkeys (Equus Asinus) Treated with Homidium and Isometamidium Chloride

“…In this study, a normocytic normochromic anaemia was observed in the group of infected untreated donkeys. The significantly higher PCV and Hb concentration recorded post treatment in the treated donkeys (Groups 3 and 4) compared to the infected untreated donkeys is suggestive of a recovery stage of the anaemic condition caused by the T, brucei brucei infection (20). Thrombocytopenia observed in this study, is similar to findings in studies on T. brucei infection in rabbits (5), and domestic and wild livestock (23).…”

“…It has been reported that the mechanism of development of anaemia in T. brucei infected animals includes a destruction of the red blood cells brought about by the lashing action of the trypanosome flagella (22). The destruction of red blood cells has also been correlated to the release of pyrogens following the fulminating parasitaemia observed in trypanosomosis (20). In this study, a normocytic normochromic anaemia was observed in the group of infected untreated donkeys.…”

“…It has been established that anaemia in trypanosomiasis is a constant and inevitablefinding, and essentially haemolytic in nature, its severity determined by virulence of the infecting trypanosomes and host susceptibility (19,20). The donkeys in group 1 (the uninfected group) which served as control for the experiment had haematologic values that were within reported haematologic reference intervals for donkeys (21).…”

Role of Cytokines in <i>Trypanosoma brucei</i>-Induced Anaemia: A Review of the Literature

“…Most studies assessed the development of anaemia by looking at the red blood cell (RBC) counts at different time points in experimentally infected mice, and comparing these counts to preinfection levels or those of controls (uninfected mice) 11,21,22 . This assessment assumes that preinfection levels were normal, with anaemia being defined as a drop in RBC count by a specified magnitude.…”

“…Overexpression of the IFN-γ gene in mice results in chronic anaemia. It is indicated that trypanosomiasis is associated with increased expression of IFN-γ, which may suppress erythropoiesis and result in anaemia 22,25 . It is also suggested that suppressed erythropoiesis is a result of apoptosis of haematopoetic progenitor cells 11 , leading to impaired red blood cell maturation.…”