Erythrophagocytosis of desialylated red blood cells is responsible for anaemia duringTrypanosoma vivaxinfection

Abstract

SummaryTrypanosomal infection-induced anaemia is a devastating scourge for cattle in widespread regions. Although Trypanosoma vivax is considered as one of the most important parasites regarding economic impact in Africa and South America, very few in-depth studies have been conducted due to the difficulty of manipulating this parasite. Several hypotheses were proposed to explain trypanosome induced-anaemia but mechanisms have not yet been elucidated. Here, we characterized a multigenic family of trans-sialidases in T. vivax, some of which are released into the host serum during infection. These enzymes are able to trigger erythrophagocytosis by desialylating the major surface erythrocytes sialoglycoproteins, the glycophorins. Using an ex vivo assay to quantify erythrophagocytosis throughout infection, we showed that erythrocyte desialylation alone results in significant levels of anaemia during the acute phase of the disease. Characterization of virulence factors such as the trans-sialidases is vital to develop a control strategy against the disease or parasite.

Evaluation of clinical signs, parasitemia, hematologic and biochemical changes in cattle experimentally infected with Trypanosoma vivax

“…There was a steady decrease in the erythrocyte count, hemoglobin and PCV, although they remained within the reference values. Decreases in erythrocytes have been associated with erythrocytes desialylation in the acute phase of disease, stage of high parasitemia (GUEGAN et al, 2013). Our findings differ from those obtained by other authors in cattle BATISTA et al, 2007BATISTA et al, , 2008CUGLOVICI et al, 2010;CADIOLI et al, 2012) who noticed moderate to severe anemia.…”

Hemophagocytic lymphohistiocytosis (HLH): A heterogeneous spectrum of cytokine-driven immune disorders

“…Both cytokines are thought to promote the development of anemia and immunopathology, but also to regulate parasitemia and prolong survival. Additionally, IL-10 is shown to mediate survival of the mice by limiting inflammatory complications, supporting a protective role for IL-10 in hyperinflammation as suggested in animal models for primary HLH [99,[104][105][106][107][108][109].…”

Production, purification and crystallization of atrans-sialidase fromTrypanosoma vivax

“…The biological role of TvTS1 is less well defined. Evidence presented by Guegan et al (2013) suggests that TvTS1 may play a role in T. vivax-associated anaemia, although this hypothesis requires further investigation. Study of the structure-function relationship of TvTS1 will help in grasping its biological function during bloodstream T. vivax parasite infections and might serve as the basis for the development of an antipathology treatment.…”

“…In T. cruzi, the only intracellular trypanosome, it has been shown that its transsialidases play a role in host-cell invasion, parasite virulence and immune suppression (Schenkman et al, 1992;Buschiazzo et al, 2002;Jacobs et al, 2010;Giorgi & de Lederkremer, 2011). In T. vivax infections, trans-sialidase activity has been proposed to be linked to the typically observed severe anaemia (Bratosin et al, 1998;Buratai et al, 2006;Guegan et al, 2013). Hence, for disease-associated trypanosomal transsialidases, unravelling their structure-function relationship might yield insights into the molecular mechanisms behind the onset of trypanosomosis-induced pathologies.…”