Extracellular vesicles of Trypanosoma cruzi and immune complexes they form with sialylated and non-sialylated IgGs increase small peritoneal macrophage subpopulation and elicit different cytokines profiles

Front Immunol. 2023 Aug 2:14:1215913. doi: 10.3389/fimmu.2023.1215913. eCollection 2023.

Abstract

American trypanosomiasis, or Chagas disease, is caused by the protozoan parasite Trypanosoma cruzi and is characterized by the presence of cardiac or gastrointestinal symptoms in a large number of patients during the chronic phase of the disease. Although the origin of the symptoms is not clear, several mechanisms have been described involving factors related to T. cruzi and the host immune response. In this sense, the extracellular vesicles (EVs) secreted by the parasite and the immune complexes (ICs) formed after their recognition by host IgGs (EVs-IgGs) may play an important role in the immune response during infection. The aim of the present work is to elucidate the modulation of the immune response exerted by EVs and the ICs they form by analyzing the variation in the subpopulations of small and large peritoneal macrophages after intraperitoneal inoculation in mice and to evaluate the role of the sialylation of the host IgGs in this immunomodulation. Both macrophage subpopulations were purified and subjected to cytokine expression analysis by RT-qPCR. The results showed an increase in the small peritoneal macrophage subpopulation after intraperitoneal injection of parasite EVs, but a greater increase in this subpopulation was observed when sialylated and non-sialylated ICs were injected, which was similar to inoculation with the trypomastigote stage of the parasite. The cytokine expression results showed the ability of both subpopulations to express inflammatory and non-inflammatory cytokines. These results suggest the role of free EVs in the acute phase of the disease and the possible role of immune complexes in the immune response in the chronic phase of the disease, when the levels of antibodies against the parasite allow the formation of immune complexes. The differential expression of interleukins showed after the inoculation of immune complexes formed with sialylated and non-sialylated IgGs and the interleukins expression induced by EVs, demonstrates that the IgG glycosilation is involved in the type of immune response that dominates in each of the phases of the Chagas disease.

Keywords: Trypanosoma cruzi; extracellular vesicles; immune modulation; interleukins; macrophages; trypomastigotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Antibody Complex
  • Chagas Disease*
  • Cytokines
  • Extracellular Vesicles*
  • Macrophages, Peritoneal
  • Mice
  • Trypanosoma cruzi*

Substances

  • Antigen-Antibody Complex
  • Cytokines

Grants and funding

This research was funded by the ERANet program, Research in prevention of congenital Chagas disease: parasitological, placental and immunological markers (ERANet17/HLH-0142 (Cochaco). Instituto Carlos III, Ministerio de Sanidad, Gobierno de Espanãa; Fundacioín Ramoín Areces “Interactoma de las exovesículas de T. cruzi y de los inmunocomplejos que forman con las células del hospedador: implicaciones en la patología de la enfermedad de Chagas (2019)”. Ministerio de Ciencia y Tecnología of the Government of Spain funded the project PGC2018-099424-B-I00)”. Exovesiculas circulantes como marcadoras de diagnostico, PREcoz de la Enfermedad de CHAGas Fundación Ramón Areces del XXI Concurso Nacional para la adjudicación de Ayudas a la Investigación en Ciencias de la Vida y de la Materia (2022). Ministerio de Ciencia y Tecnologiía of the government of Spain funded the project PGC2018-099424-B-I00.