La brucelosis es una enfermedad zoonótica causada por bacterias del género Brucella, distribuida a nivel mundial. A pesar de los programas de erradicación, la brucelosis sigue siendo un problema serio para la salud pública y para la ganadería. Por ello, el conocimiento de los mecanismos y estrategias empleados por B. abortus para persistir en el hospedador es crucial para el diseño de vacunas y tratamientos eficaces para el control de la enfermedad. A su vez, dichas estrategias de evasión inmune podrían extrapolarse al contexto de otras infecciones intracelulares y tumores.
Directora: Dra. Paula Barrionuevo
Investigadora Independiente CONICET
Email: pbarrion2004@yahoo.com.ar, pbarrion2009@gmail.com
- Lic. Agustina Serafino. Becaria de Finalización de Doctorado CONICET. Directora: Dra. Paula Barrionuevo, Co-Directora: Dra. María Ayelén Milillo.
- Lic. Yasmín Ayelén Bertinat. Becaria Doctoral ANPCyT. Directora: Dra. Paula Barrionuevo
- Jorgelina Bueno. Estudiante Ciencias Biológicas, FCEN, UBA. Directora: Dra. Paula Barrionuevo
- Dra. Barbara Rearte
- Jessica Rocca
- Mailen Di Palma
Nuestro grupo de trabajo se encuentra desarrollando las siguientes líneas de investigación:
1) Estrategias de evasión inmune mediadas por Brucella abortus (una bacteria intracelular patógena para el humano y el ganado) sobre linfocitos T y macrófagos.
2) Crosstalk entre plaquetas, B. abortus y células inmunes: su rol en la infección y la inmunopatología de la brucelosis humana.
3) Estudio del rol del ARN bacteriano sobre la modulación inmune en contextos tumorales en los cuales las respuestas de linfocitos T CD8+ y NK son clave.
1. Pittaluga JR, Birnberg-Weiss F, Serafino A, Castro JE, Castillo LA, Martire-Greco D, Barrionuevo P, Fernández GC, Landoni VI. The RNA from Pseudomonas aeruginosa reduces neutrophil responses favoring bacterial survival. Journal of Innate Immunity, 16 (1): 489–500, 2024. https://doi.org/10.1159/000541414
2. 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, 19(7): e0306429, 2024. https://doi.org/10.1371/journal.pone.0306429
3. 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
4. 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
5. 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
6. 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
7. 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.
8. 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): 708, 2020. *These authors have contributed equally to this work. ** These authors share senior authorship. doi: 10.3390/pathogens9090708.
9. 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.
10. Milillo MA, Trotta A, Serafino A, Marin Franco JL, 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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. doi: 10.1371/journal.ppat.1006527.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.