Trypanosoma cruzi amastigote adhesion to macrophages is facilitated by the mannose receptor.

Abstract

SummaryTrypanosoma cruzi is an obligate intracellular protozoan parasite. The mammalian stage of the parasite life cycle describes amastigotes as an intracellular form that replicates, and trypomastigotes as an extracellular form that disseminates and invades cells. Recent studies, however, have demonstrated that amastigotes circulate in the blood of infected mammals and can invade mammalian cells. In this report, a T. cruzi surface glycoprotein gene, SA85-1.1, was expressed as an immunoglobulin chimera, and this recombinant globulin was used to screen normal mouse tissues for adhesive interactions. This approach identified a subset ofmacrophages in the skin and peripheral lymph node that bind the T. cruzi surface glycoproteins through the mannose receptor. To further examine the T. cruzi mannose receptor carbohydrate ligands, the interaction between T. cruzi and the mannose-binding protein, a mammalian lectin with similar carbohydrate binding specificities as the mannose receptor, was examined. These studies demonstrated that the mannose-binding protein recognized amastigotes, but not trypomastigotes or epimastigotes, and suggested that amastigotes would also be recognized by the rnannose receptor. Therefore, amastigote adhesion to macrophages was investigated, and these experiments demonstrated that the mannose receptor contributes to amastigote adhesion. The data identify the first mammalian lectins that bind to T. cruzi, and are involved in T. cruzi invasion of mammalian cells. The data suggest that amastigotes and trypomastigotes may have developed different mechanisms to adhere to and invade host cells. In addition, it has been established that IFN-',/-activated macrophages express low levels of the mannose receptor and are trypanocidal; this suggests that the interaction between amastigotes and the mannose receptor enables amastigotes to increase their adherence with a population ofmacrophages that are nontrypanocidal and permissive for their intracellular replication.

Immunization with cDNA Expressed by Amastigotes ofTrypanosoma cruziElicits Protective Immune Response against Experimental Infection

“…Members of subfamily II have been shown to be expressed in both trypomastigotes and amastigotes of T. cruzi (6,8,16,20,27,33,34,36). RT-PCR analyses using specific primers showed FIG.…”

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

“…These surface antigens are a highly polymorphic family of proteins with molecular masses ranging from 85 to 200 kDa. Many of these proteins have been implicated in a number of biological processes important for T. cruzi interaction with host cells and extra-cellular matrix proteins (6)(7)(8)(9)(10)(11). One group of these proteins are enzymes denominated transsialidase (TS) that catalyze the transfer of sialic acid to ß-galactosyl residues of mucinlike glycoproteins that are present on the surface of T. cruzi trypomastigotes and epimastigotes (12,13).…”

Immunocharacterization of the mucin-type proteins from the intracellular stage of Trypanosoma cruzi

“…The presence of a mosaic of mucin-like products displaying different HV-peptides might be relevant for the parasite-host interplay and deserves further analyses. Since T. cruzi amastigotes were shown to circulate in the bloodstream and to infect macrophages [29], one possibility would be that this surface heterogeneity might help in facing the immune pressure exerted by the infected host, as proposed for bloodstream trypomastigotes [17]. A further possibility would be that these HV-peptides influence antigen presentation in the context of the histocompatibility complex of infected cells.…”