Toxoplasma gondiiAntigen-Pulsed-Dendritic Cell-Derived Exosomes Induce a Protective Immune Response againstT. gondiiInfection

Abstract

It was previously demonstrated that immunizing mice with spleen dendritic cells (DCs) that had been pulsed ex vivo with Toxoplasma gondii antigens triggers a systemic Th1-biased specific immune response and induces protection against infection. T. gondii can cause severe sequelae in the fetuses of mothers who acquire the infection during pregnancy, as well as life-threatening neuropathy in immunocompromised patients, in particular those with AIDS. Here, we investigate the efficacy of a novel cell-free vaccine composed of DC exosomes, which are secreted antigen-presenting vesicles that express functional major histocompatibility complex class I and II and T-cell-costimulatory molecules. They have already been shown to induce potent antitumor immune responses. We investigated the potential of DC2.4 cell line-derived exosomes to induce protective immunity against toxoplasmosis. Our data show that most adoptively transferred T. gondii-pulsed DC-derived exosomes were transferred to the spleen, elicited a strong systemic Th1-modulated Toxoplasma-specific immune response in vivo, and conferred good protection against infection. These findings support the possibility that DC-derived exosomes can be used for T. gondii immunoprophylaxis and for immunoprophylaxis against many other pathogens.

Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells

“…5, Rv1818c protein can be detected in exosomes derived from infected BM-DC's or RAW macrophages but not in exosomes from uninfected cells. In addition, consistent with earlier findings [26], a homogenous population of vesicles 60 to 150 nm in diameter was observed by electron microscopy (supplementary data Appendix no. 5).…”

“…BM-DCs were generated as described previously [26]. Briefly, bone marrow cells were cultured cultured for 24 h in complete medium (RPMI 1640 containing 10% FBS, 50 mM 2-ME, 2 mM glutamine, 0.1 mM non-essential amino acids, 100 mg/ml streptomycin, and 100 IU/ml penicillin) to remove the adherent macrophages.…”

“…BM-DC's and RAW 264.7 macrophages were infected with Mycobacterium tuberculosis H37Ra at an MOI of 50:1 and the exosomes were prepared from the cell culture supernatant by differential centrifugation as described previously [26,27]. Briefly, recovered culture supernatant from each BM-DC or RAW 264.7 culture was subjected to three successive centrifugations at 300 Â g (5 min), 1200 Â g (20 min), and 10,000 Â g (30 min), followed by centrifugation for 1 h at 100,000 Â g. The exosome pellet was washed with a large volume of PBS.…”

Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis

“…Exosomes have received great attention lately owing to their potential to induce immune responses or tolerance,10 depending on their cellular origin. Exosomes loaded with tumour antigens are considered as promising vaccine candidates in cancer11 12 and infectious diseases such as toxoplasmosis 13. In 2003 our group isolated exosomes from BALF (BALF exosomes)14 which had phenotypic similarities to DC-derived exosomes.…”

The secretome of mesenchymal stromal cells: Role of extracellular vesicles in immunomodulation

“…Macrophages infected with Mycobacterium release EVs containing pathogen-derived pro-inflammatory molecules, inducing the secretion of pro-inflammatory cytokines [31]. EVs secreted by DCs are able to induce humoral responses against antigens processed by DCs before EVs purification, leading to strong protection against infection [32,33]. DC-derived EVs can shuttle both antigenic materials and MHC-peptide complexes, that can be presented to T lymphocytes.…”