Experimental Immunology

• Mercedes Pastorini, MSc. Doctoral students – CONICET.

SAGs and Virus-Like Particles with Junin Virus Z Protein (Z-VLP) as a Therapeutic Tool

Superantigens (SAgs) are proteins of viral or bacterial origin that bind to the non-polymorphic region of MHCII outside the groove where conventional peptides are presented. These SAgs have the ability to induce apoptosis of lymphocytes carrying a specific variable region in vitro and in vivo. We study the effect of SAgs on the elimination of leukemic cells from patients in culture and in a Nod/SCID mouse model, aiming to develop a new therapeutic approach for human lymphomas/leukemias. Additionally, we assess the adjuvant and immunogenic capacity of the Junin virus Z protein to generate VLPs containing eGFP as a model antigen, for use as platforms by cloning different antigens. Currently, we are designing a VLP platform that carries different SAgs fused with the Junin Z protein to induce specific elimination of lymphomas/leukemias.

Innate Immunity in Tuberculosis

We investigate the relevance of host-pathogen interaction in the immune response, analyzing the involvement of certain Pathogen-Associated Molecular Patterns (PAMPs) and Pattern Recognition Receptors (PPRs) in the immune response to tuberculosis. Currently, we are studying a single nucleotide polymorphism (SNP) (Y238X, rs16910526) in the host, which introduces a stop codon in dectin-1, resulting in the loss of the last 9 amino acids of the recognition domain, and its possible association with the generation of Reactive Oxygen Intermediates (ROS) and tuberculosis disease. On the other hand, we evaluate the role of α-glucans from the capsule of M. tuberculosis, which are involved in ROS generation, using genetically modified variants of Mtb H37Rv (ΔtreSu-ΔglgB, ΔtreSu-ΔglgE, and ΔtreSu-ΔglgC) lacking key enzymes in the α-glucan synthesis pathways.

1. Duarte A, Montagna D, Pastorini M, Alemán M. Apoptosis-mediated inhibition of human T-cell acute lymphoblastic leukemia upon treatment with Staphylococus Aureus enterotoxin-superantigen. Frontiers Immunology (2023) doi: 10.3389/fimmu.2023.1176432
2. Alemán, M. “The Good, the Bad and the Ugly”: Interplay of Innate Immunity and Inflammation. Cell Microbiol Vol 2022 doi.org/10.1155/2022/2759513
3. Romero MM, Duarte A, Pastorini M, Alemán M. Role of α-glucans from Mycobacterium tuberculosis in dendritic cell response against tuberculosis. Int. J. Med. Microbiol. (2019) https://doi.org/10.1016/j.ijmm.2019.07.002
4. Romero MM, Basile JI, Corra Feo L, López B, Ritacco V, Alemán M. Reactive oxygen species production by human dendritic cells involves TLR2 and dectin-1 and is essential for efficient immune response against Mycobacteria. Cell Microbiol. 2016 Dec 28. PMID: 26709456. doi: 10.1111/cmi.12562.
5. Lorenzo D, Duarte A, Mundiñano Juliana, Berguer Paula, Nepomnaschy Irene and Piazzon Isabel. A B-cell superantigen induces the apoptosis of murine and human malignant B cell. PLoS One 2016 Sep 7;11(9): e0162456.
6. Alemán M. Neutrophil apoptosis in the context of tuberculosis infection. Tuberculosis (Edinb). 2015 Jul;95(4): 359-63. PMID: 25864404. doi: 10.1016/j.tube.2015.03.010.
7. Romero MM, Basile JI, López B, Ritacco V, Barrera L, Sasiain M del C, Alemán M. Outbreaks of Mycobacterium tuberculosis MDR strains differentially induce neutrophil respiratory burst involving lipid rafts, p38 MAPK and Syk. BMC Infect Dis. 2014 May 16;14: 262. PMID:24886274. doi: 10.1186/1471-2334-14-262.
8. Balboa L, Romero MM, Laborde E, Sabio Y García CA, Basile JI, Schierloh P, Yokobori N, Musella RM, Castagnino J, de la Barrera S, Sasiain MC, Alemán M. Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK. Eur J Immunol. 2013 Feb;43(2): 335-47. PMID:23192690. doi: 10.1002/eji.201242557.Romero MM, Balboa L, Basile JI, López B, Ritacco V, de la Barrera SS, Sasiain MC, Barrera L, Alemán M. Clinical isolates of Mycobacterium tuberculosis differ in their ability to induce respiratory burst and apoptosis in neutrophils as a possible mechanism of immune escape. Clin Dev Immunol. 2012; 2012:152546. Epub 2012 Jun 21. PMID: 22778761. doi: 10.1155/2012/152546.

1. Latin American International Award in Pulmonology ”Fernando D. Gómez – Miguel Mello Aguerre” 2023. “Polimorfismos en DECTIN-1 y la infección tuberculosa”. M Cufré, DJ Palmero, M Pastorini, M Alemán.
2. Eufemio Uballes Award: For the best work in «Experimental Research: Clinical or Therapeutic» contributing to the progress of knowledge in the fight against cancer. Alejandra Duarte, Daniela Montagna, Mercedes Pastorini, Raúl Ruggiero, Mercedes Alemán. 2023.
3. First Mention by Merit of the Florencio Fiorini Annual Award 2023: For advances in respiratory diseases. Mónica Cufré, Domingo Palmero, Alejandra Duarte, Mercedes Pastorini, Ignacio Martín, Rodrigo Failde. 2023.
4. Science in Action Award: Selected work. Barcelona 2019.
5. Latin American International Award in Pulmonology «Fernando D. Gómez» 2018: María Mercedes Romero, Viviana Ritacco, Beatriz López, Mercedes Alemán.
6. Best Poster Award: SAI-SAIC-SAFE: A B-cell superantigen induces the apoptosis of murine and human malignant B cells. Alejandra Duarte, Daniela Lorenzo, Juliana Mundiñano, Paula Berger, Alejandro Sielecki, Mercedes Alemán, Irene Nepomaschi, Isabel Piazzón. Annual Meeting of the Argentine Society of Clinical Research. Buenos Aires, Argentina. 2016.
7. Latin American International Award in Pulmonology «Fernando D. Gómez» 2012: Variation in the respiratory burst and apoptosis of human neutrophils by clinical isolates of Mycobacterium tuberculosis, as a possible mechanism of evasion of the immune response. María Mercedes Romero, Juan Ignacio Basile, Viviana Ritacco, Beatriz López, Lucía Barrera, Mercedes Alemán.
8. Latin American International Award in Pulmonology «Fernando D. Gómez» 2014: Mechanisms involved in the generation of reactive oxygen intermediates in PMN in response to Mycobacterium tuberculosis. María Mercedes Romero, Laura Correa Feo, Viviana Ritacco, Beatriz López, Mercedes Alemán.