Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents

Abstract

Vespa et al., 1994;Biron and Gazzinelli, 1995 Aliberti et al., 1996;Fearon and Locksley, 1996; Trinchieri and Scott, 1996). In addition, the early Seder et al., 1993; Abbas et al., 1996; Fearon macrophage proinflammatory cytokines by Trypanoand Locksley, 1996). During infection with T.cruzi, the soma cruzi is considered to be important in controlling induction of parasite-specific CMI is likely to be involved the infection and the outcome of Chagas' disease. Here in at least two aspects of Chagas' disease pathophysiology we show that the potent tumour necrosis factor-α-, (Vespa et al., 1994;Fearon and Locksley, 1996; Brener interleukin-12-and nitric oxide-inducing activities of and Gazzinelli, 1997). The first is the control of parasite T.cruzi trypomastigote mucins were recovered quantireplication and its spread in the vertebrate host tissues. tatively in a highly purified and characterized glycosyl-The second is the inflammatory reaction observed in the phosphatidylinositol (GPI) anchor fraction of this infected host tissues, which is likely to be a major cause material. The bioactive trypomastigote GPI fraction of cardiac tissue damage during the acute and chronic was compared with a relatively inactive GPI fraction phases of the disease. prepared from T.cruzi epimastigote mucins. The trypoRelatively little is known about the protozoan parasite mastigote GPI structures were found to contain addimolecules that initiate the synthesis of pro-inflammatory tional galactose residues and unsaturated, instead of cytokines and nitric oxide (NO) by macrophages. Recent saturated, fatty acids in the sn-2 position of the alkylstudies have suggested a role for glycosylphosphatidylacylglycerolipid component. The latter feature is esseninositol (GPI) anchors from Plasmodium falciparum tial for the extreme potency of the trypomastigote (Schofield and Hackett, 1993;Schofield et al., 1996; GPI fraction, which is at least as active as bacterial Tachado et al., 1996Tachado et al., , 1997 and Trypanosoma brucei endotoxin and Mycoplasma lipopeptide and, therefore, (Magez et al., 1998) in this process. However, no evidence one of the most potent microbial proinflammatory of the biochemical purity of the P.falciparum GPIs was agents known.provided, making estimates of their concentrations dubiKeywords: Chagas' disease/cytokines/glycosylphosphaous. Furthermore, the possibility of Mycoplasma lipopeptidylinositol/inflammation/nitric oxide tide (Mühlradt et al., 1997) contamination (that has confounded other studies into proinflammatory factors) cannot be formally excluded. In the case of the T.brucei GPI work, highly purified and structurally characterized

Lack of antigen-specific Th1 response alters granuloma formation and composition inSchistosoma mansoni-infected MyD88-/- mice

“…In Toxoplasma gondi-, Trypanosoma cruzi-and Leishmania major-infected MyD88 -/-mice, the absence of IFN-c production by primed lymphocytes upon recall with the respective antigen correlated with the failure of APC to produce IL-12 upon co-incubation with protozoan antigens [36][37][38][39]. In a recent study, IL-12 and TNF-a production by DC when co-incubated with whole S.…”

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells

“…Similar to whole parasite, YuYu EVs were enriched with TS family of glycoproteins, mucins, and mucin-associated proteins when compared to those from Y strain. Those molecules are well-established T. cruzi virulence factors [1,5,7,8,30–34]. Both strains were able to release EVs suggesting that similar mechanisms of their biogenesis may occur among different T. cruzi groups [18,35].…”

“…Those molecules are involved in attachment and invasion to the host’s cell by infective forms of the parasite [4–6]. Previous reports showed that some of those molecules may act as proinflammatory agents during the innate immune response [7] leading to the production of nitric oxide (NO),IL-6, IL-12, and TNF-α via TLR2 by macrophages [7,8]. Major parasite surface components, such as TS/gp85 glycoproteins, mucins, and surface proteases GP63, were found in extracellular vesicles (EVs) shed by infective trypomastigote forms of the parasite [9,10].…”

More than just exosomes: distinct Leishmania infantum extracellular products potentiate the establishment of infection

“…Lipophosphoglycan (LPG) is a TLR2 agonist capable of activating mouse macrophages and human NK cells, in a MyD88-dependent manner [42–44]. Also, glycosylphosphatidylinositol, that in T. cruzi activates TLR2 and TLR4 [45–47], might be a PAMP present among Leishmania extracellular products. Even proteins might have unexpected capacities to interact with TLRs, as L. infantum Sir2 was demonstrated to induce the maturation of DCs in a TLR2-dependent manner with the secretion of IL-12 and TNF-α [48].…”