Chapter category: Infectious Disease
Trypanosoma cruzi trans-Sialidase: A Cytokine Mimetic (Parasitokine)
Molecular Mechanisms of Pathogenesis in Chagas Disease
Edited by: JohnM. KellyISBN: 0-306-47849-8
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Chapter authors:
Wenda Gao and Miercio A. Pereira
Cytokines are small soluble proteins with high potency in orchestrating host immune responses during stress, injury, tumorgenesis, and infection. Studies in animal models and humans have generated a large body of evidence correlating specific antiparasite immune responses with cytokine patterns. For instance, control of intracellular pathogens requires cellular immune responses mediated by type 1 cytokines (IL2, IFNg and others) while control of extracellular pathogens necessitates humoral immune responses accompanied by preferential type 2 cytokines (IL4 and others). Cytokine profiles arise as a consequence of the antigenic nature of parasite molecules exposed to the host immune system. However, the harmony of cytokine secretion can be sabotaged by the parasites through molecular mimicry. It is well known that some viruses encode soluble molecules structurally and functionally similar to antiinflammatory cytokines and proinflammatory cytokine receptors, named virokines and viroceptors, respectively. A novel concept that protozoan and worm parasites can produce molecules structurally and/or functionally akin to host cytokines, named parasitokines, is emerging. We describe here four model parasitokines derived from three distinct parasites: 1) Trypanosoma cruzi: trans-sialidase (TS), an inducer of cytokine secretion in normal endothelial cells and immune cells, of immunoglobulin production in normal B lymphocytes, and of T lymphocyte activation through antigenpresenting cells. 2) T. cruzi: proline racemase, a polyclonal activator of B lymphocytes. 3) Trypanosoma brucei: T lymphocyte triggering factor (TLTF), a polyclonal activator of CD8+ T lymphocytes and an inducer of IFNg, a cytokine that promotes growth of T. brucei. And 4) Brugia malayi: BmMIF, a 12.5 kDa peptide homologue of macrophage migration inhibitory factor (MIF). Parasitokines, like conventional cytokines, could be important promoters of parasitism. Indeed, experiments in vivo showed that TS can enhance virulence of T. cruzi and of transgenic Leishmania major.
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Trypanosoma cruzi trans-Sialidase: A Cytokine Mimetic (Parasitokine)
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