A Non-Cytosolic Protein of Trypanosoma evansi Induces CD45-Dependent Lymphocyte Death

Abstract

In a recent study dealing with a mouse model of Trypanosoma evansi-associated disease, a remarkable synchrony between the parasitaemia peak and the white-blood-cell count nadir was noticed. The present study was designed to establish whether there is a direct causal link between the parasite load during its exponential phase of growth and the disappearance of peripheral blood leukocytes. In vitro experiments performed with trypanosomes and purified peripheral blood mononucleated cells revealed the existence of a lymphotoxin embedded in the T. evansi membrane: a protein sensitive to serine proteases, with a molecular mass of less than 30 kDa. Lymphocytes death induced by this protein was found to depend on the intervention of a lymphocytic protein tyrosine phosphatase. When lymphocytes were exposed to increasing quantities of a monoclonal antibody raised against the extracellular portion of CD45, a transmembrane protein tyrosine phosphatase covering over 10% of the lymphocyte surface, T. evansi membrane extracts showed a dose-dependent decrease in cytotoxicity. As the regulatory functions of CD45 concern not only the fate of lymphocytes but also the activation threshold of the TCR-dependent signal and the amplitude and nature of cytokinic effects, this demonstration of its involvement in T. evansi-dependent lymphotoxicity suggests that T. evansi might manipulate, via CD45, the host's cytokinic and adaptive responses.

Trypanosoma evansiand Surra: A Review and Perspectives on Origin, History, Distribution, Taxonomy, Morphology, Hosts, and Pathogenic Effects

“…These results suggest that at least in a mouse model, trypanosomes are capable of permanently destroying the host B-cell memory compartment, in a nonantigen specific manner [192]. In the same way, it has been proved recently that a T. evansi lymphotoxin is able to induce CD45-dependent lymphocyte death [193], which correlates with pioneering findings demonstrating that membrane fractions of T. evansi elicit suppressor cells [194]. …”

Gross and Histopathological Alterations in Experimental Trypanosoma Evansi Infection in Donkeys and the Effect of Isometamidium Chloride Treatment

“…The histopathological findings in T. evansi-infected, untreated group of animals at termination of this experiment on day 176 PI (chronically) were severe forms of lung congestion and mononuclear cellular infiltration due to vascular stasis in lungs and liver, splenic haemosiderosis due to deposits of free iron from severe intravascular hemolysis, RBC sequestration in the red pulp area as reported by Bal et al and cells lysis by T. evansi lymphotoxins also contribute to iron deposits in tissues [43,44]. Depletion of lymphocytes at germinal centres, severe hepatic congestion, the moderate forms of hepatic focal areas of necrosis and mononuclear cellular infiltrations the prominent lesions also reported from other parts of the world [43].…”

Molecular cloning of IgT from Atlantic salmon, and analysis of the relative expression of τ, μ and δ in different tissues

“…Transcriptomic responses to lice were also characterised by an early increase of T cell specific transcripts in the skin, which totally ceases after day 5. Their functional roles remain to be identified, while a number of questions were raised including from where they originate -Moussiaux et al, 2009). Due to the enormous abilities of parasites to trigger highly polarized CD4+ T cell subset responses, which depends on the host genetic background, T lymphocyte-parasite interactions have been regarded as crucial subjects of research (Jankovic et al, 2001;Sher and Coffman, 1992).…”