Las bacterias del género Brucella son el agente etiológico de la brucelosis, una zoonosis presente en todo el mundo y la cual se caracteriza por tener un importante componente inflamatorio. Brucella abortus es un patógeno intracelular capaz de sobrevivir dentro de macrófagos. Sin embargo, Brucella puede persistir dentro de los mismos, estableciendo una infección crónica.
Directora: Dra. Paula Barrionuevo
Investigadora Independiente CONICET
Email: pbarrion2004@yahoo.com.ar, pbarrion2009@gmail.com
- Dra. Bárbara Rearte Investigadora Adjunta CONICET
- Dra. María Ayelén Milillo Investigadora Asistente CONICET.
- Lic. Agustina Serafino. Becaria Doctoral CONICET. Directora: Dra. Paula Barrionuevo. Co-Directora: Dra. María Ayelén Milillo
- Lic. Yasmín Ayelén Bertinat. Becaria Doctoral ANPCyT. Directora: Dra. Paula Barrionuevo
- Lic. Jéssica Rocca. Becaria Doctoral CONICET. Directora: Dra. Bárbara Rearte
- Jorgelina Bueno. Estudiante Ciencias Biológicas, FCEN, UBA. Directora: Dra. Paula Barrionuevo
- Lautaro Maceira. Estudiante Biotecnología, UNSAM. Directora: Dra. Bárbara Rearte
- Mailén Di Palma. Estudiante Bioquímica, FFyB, UBA. Directora: Dra. Bárbara Rearte
El objetivo general de nuestro grupo de trabajo es estudiar las estrategias y mecanismos de evasión empleados por B. abortus sobre los monocitos/macrófagos y linfocitos T, para evadir la vigilancia inmunológica y persistir crónicamente en el hospedador. Nuestra nueva línea de trabajo es estudiar también los trastornos plaquetarios observados durante la enfermedad. Por otro lado, dentro de nuestro grupo de trabajo la Dra. Bárbara Rearte investiga las estrategias que permiten revertir la inmunosupresión inducida por SIRS (Systemic Inflammatory Response Syndrom), especialmente por endotoxinas bacterianas (LPS), como una forma más racional de enfocar el problema de las sepsis inducidas por bacterias Gram negativas -portadoras de LPS- y que, eventualmente, permita la recuperación de la función inmune y plantearse estrategias terapéuticas más adecuadas para esos pacientes.
- Serafino A, Bertinat YA, Bueno J, Pittaluga JR, Birnberg Weiss F, Milillo MA*, Barrionuevo P*. Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced expression of MHC-I in epithelial and endothelial cells. *These authors have contributed equally to this work. PLoS ONE, 2024. https://doi.org/10.1371/journal.pone.0306429
- Barbero AM, Hernández Del Pino RE, Fuentes F, Barrionuevo P, Pasquinelli V. Platelets promote human macrophages-mediated macropinocytosis of Clostridioides difficile. Frontiers in Cellular and Infection Microbiology, 13:1252509, 2024. https://doi.org/10.3389/fcimb.2023.1252509
- Ledesma M, Todero MF, Maceira L, Prieto M, Vay C, Galas M, López B, Yokobori N, Rearte B. Peptidome profiling for the immunological stratification in sepsis: a proof of concept study. Sci Rep, 12(1):11469, 2022. https://doi.org/10.1038/s41598-022-15792-5
- Serafino A, Marin Franco JL, Maio M, Trotta A, Genoula M, Castillo LA, Birnberg Weiss F, Pittaluga JR, Balboa L, Barrionuevo P*, Milillo MA*. Brucella abortus RNA does not polarize macrophages to a particular profile but interferes with M1 polarization. PLoS Neglected Tropical Diseases, 16(11): e0010950, 2022. *These authors have contributed equally to this work. https://doi.org/10.1371/journal.pntd.0010950
- Milillo MA, Velásquez LV, Barrionuevo P. Microbial RNA, the new PAMP of many faces. Mini Review. Frontiers in Tropical Diseases, 3, 2022. https://doi.org/10.3389/fitd.2022.924719
- Barbero AM, Trotta A, Genoula M, Hernández Del Pino RE, Estermann MA, Celano J, Fuentes F, García VE, Balboa L, Barrionuevo P, Pasquinelli V. SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages. Journal of Leukocyte Biology, 109(1): 257-273, 2021. https://doi.org/10.1002/jlb.4ma0820-655rr
- Pineda GE, Rearte B, Todero MF, Bruballa AC, Bernal AM, Fernández-Brando RJ, Isturiz MA, Zotta E, Dirney Alba-Soto C, Palermo MS, Ramos MV. Absence of interleuquin-10 reduces progression of shiga toxin-induced hemolytic uremic syndrome. Clin Sci (Lond), 135(3): 575-588, 2021. doi: 10.1042/CS20200468.
- Ledesma M, Todero MF, Maceira L, Prieto M, Vay C, Galas M, López B, Yokobori N, Rearte B. Plasma mass spectrometry fingerprints induced by bacterial endotoxins in murine models as markers of pathophysiological evolution in sepsis. En Revisión CCMED-D-21-01262. Preprint. bioRixiv 2020.12.29.424724; doi: https://doi.org/10.1101/12.29.424724.
- Barbero AM, Trotta A, Genoula M, Hernández Del Pino RE, Estermann MA, Celano J, Fuentes F, García VE, Balboa L, Barrionuevo P, Pasquinelli V. SLAMF1 signaling induces Mycobacterium tuberculosis uptake leading to endolysosomal maturation in human macrophages. Journal of Leukocyte Biology. 2020. doi: 10.1002/JLB.4MA0820-655RR.
- Genoula M, Marín Franco JL, Maio M, Dolotowicz B, Ferreyra M, Milillo MA, Mascarau R, Moraña EJ, Palmero D, Matteo M, Fuentes F, López B, Barrionuevo P, Neyrolles O, Cougoule C, Lugo-Villarino G, Vérollet C, Sasiain MC, Balboa L. Fatty acid oxidation of alternatively activated macrophages prevents foam cell formation, but Mycobacterium tuberculosis counteracts this process via HIF-1α activation. PLoS Pathogens, 16(10): e1008929, 2020. doi: 10.1371/journal.ppat.1008929.
- Rodriguez AM*, Trotta A*, Melnyczajko AP, Miraglia MC, Kim KS, Delpino MV, Barrionuevo P**, Giambartolomei GH**. Brucella abortus-stimulated platelets activate brain microvascular endothelial cells increasing cell transmigration through the Erk1/2 pathway. Pathogens, 9(9): E708, 2020. *These authors have contributed equally to this work. ** These authors share senior authorship. doi: 10.3390/pathogens9090708.
- Trotta A, Milillo MA, Serafino A, Castillo LA, Birnberg Weiss F, Delpino MV, Giambartolomei GH, Fernández GC, Barrionuevo P. Brucella abortus-infected platelets modulate the activation of neutrophils. Immunology and Cell Biology, 98(9): 743-756, 2020. doi: 10.1111/imcb.12373.
- Montagna D, Duarte A, Todero MF, Ruggiero R, Isturiz M, Rearte B. Meta-tyrosine modulate the immune response and immunosuppression induced by bacterial endotoxins. Immunobiology, 225(1), 151856, 2020. doi:10.1016/j.imbio.2019.10.005.
- Yokobori N, Monteserin J, Rearte B, Paul R, Símboli N, López B, Ritacco V, Sasiain MC. Survival of an epidemic MDR strain of Mycobacterium tuberculosis and its non-prosperous variant within activated macrophages. Infection, Genetics and Evolution, 73, 248–254, 2019.
- Milillo MA, Trotta A, Serafino A, Marinho FV, Alcain J, Genoula M, Balboa L, Oliveira SC, Giambartolomei GH*, Barrionuevo P*. Brucella abortus RNA contributes to the down-modulation of MHC-II expression on monocytes/macrophages diminishing CD4+ T cell responses. Frontiers in Immunology, 10: 2181, 2019. *These authors contributed equally to this work. doi: 10.3389/fimmu.2019.02181.
- Barrionuevo P and Giambartolomei GH. Inhibition of antigen presentation by Brucella: many more than many ways. Review. Microbes and Infection, pii: S1286-4579(19)30002-4, 2019.
- Córdoba-Moreno MO, Todero MF, Fontanals A, Pineda G, Ramos MV, Isturiz MA, Rearte B. Consequences of the lack of IL-10 in different endotoxin effects and its relationship with glucocorticoids. SHOCK, 52 (2): 264–273, 2018.
- Miraglia MC, Rodriguez AM, Barrionuevo P, Rodriguez J, Kim KS, Dennis VA, Delpino MV, Giambartolomei GH. Brucella abortus traverses brain microvascular endothelial cells using infected monocytes as a trojan horse. Frontiers in Cellular and Infection Microbiology, 8: 200, 2018. doi: 10.3389/fcimb.2018.00200.
- Trotta A, Velásquez LN*, Milillo MA*, Delpino MV, Rodríguez AM, Landoni VI, Giambartolomei GH, Pozner RG, Barrionuevo P. Platelets promote Brucella abortus monocyte invasion by establishing complexes with monocytes. Frontiers in Immunology, 9: 1000, 2018. *These authors contributed equally to this work. doi: 10.3389/fimmu.2018.01000.
- Genoula M, Marín Franco JL, Dupont M, Kviatcovsky D, Milillo A, Schierloh P, Moraña EJ, Poggi S, Palmero D, Mata-Espinosa D, González-Domínguez E, León Contreras JC, Barrionuevo P, Rearte B, Córdoba Moreno MO, Fontanals A, Crotta Asis A, Gago G, Cougoule C, Neyrolles O, Maridonneau-Parini I, Sánchez-Torres C, Hernández-Pando R, Vérollet C, Lugo-Villarino G, Sasiain MC, Balboa L. Formation of foamy macrophages by tuberculous pleural effusions is triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 axis through ACAT upregulation. Frontiers in Immunology, 9: 459, 2018. doi: 10.3389/fimmu.2018.00459.
- Milillo MA, Velásquez LN, Trotta A, Delpino MV, Marinho FV, Balboa L, Vermeulen M, Espindola S, Rodriguez-Rodrigues N, Fernández GC, Oliveira SC, Giambartolomei GH, Barrionuevo P. B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway. PLoS Pathogens, 13(8): e1006527, 2017.
- Rodriguez-Rodrigues N, Castillo L, Landoni VI, Martire-Greco D, Milillo MA, Barrionuevo P, Fernández GC. Prokaryotic RNA associated to bacterial viability induces polymorphonuclear neutrophil activation. Frontiers in Cellular and Infection Microbiology, 7: 306, 2017.
- Rodriguez AM, Delpino MV, Miraglia MC, Costa Franco MM, Barrionuevo P, Dennis VA, Oliveira SC, Giambartolomei GH. Brucella abortus-activated microglia induce neuronal death through primary phagocytosis. Glia, 65(7): 1137-1151, 2017.
- Velásquez LN*, Milillo MA*, Delpino MV, Trotta A, Mercogliano MF, Pozner RG, Schillaci R, Elizalde PV, Giambartolomei GH, Barrionuevo P. Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway. Immunology and Cell Biology, 95(4): 388-398, 2017. *These authors contributed equally to this work.
- Velásquez LN, Milillo MA, Delpino MV, Trotta A, Fernández P, Pozner RG, Lang R, Balboa L, Giambartolomei GH, Barrionuevo P. Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the down-modulation of IFN regulatory factor-1 (IRF-1). Journal of Leukocyte Biology, 101(3): 759-773, 2017.
- Coria LM, Ibañez AE, Tkach M, Sabbione F, Bruno L, Carabajal MV, Berguer PM, Barrionuevo P, Schillaci R, Trevani AS, Giambartolomei GH, Pasquevich KA, Cassataro J. A Brucella spp. protease inhibitor limits antigen lysosomal proteolysis, increases cross-presentation, and enhances CD8+ T cell responses. Journal of Immunology, 196(10): 4014-29, 2016.
- Miraglia MC, Costa Franco MM, Rodriguez AM, Bellozi PM, Ferrari CC, Farias MI, Dennis VA, Barrionuevo P, de Oliveira AC, Pitossi F, Kim KS, Delpino MV, Oliveira SC, Giambartolomei GH. Glial cell-elicited activation of brain microvasculature in response to Brucella abortus infection requires ASC inflammasome-dependent IL-1β production. Journal of Immunology, 196(9): 3794-805, 2016.