Neuroimmunology

PROFILE

Emerging evidence shows the existence of diverse physical and functional interactions between the immune and nervous systems. The nervous system may regulate the immune response and its potency against viral and bacterial infections and tumour development. Similarly, the immune system appears to be able to regulate some functions of the nervous system including processes involved in behavior, learning and memory. Due to the existence of this bidirectional cross-talk between these two systems, the deregulation of neuro-immune communications could result in immune-related diseases or in neurological/psychiatric associated disorders. The primary aim of our research is to understand the mechanisms operating in neuro-immune communications and thus to determine how stimulation of some pathways in the nervous system may potentiate or inhibit immune responses during infectious diseases, cancer and autoimmunity. We also aim to understand how the activity of specific immunological components may regulate some cognitive tasks or contribute in the physiopathologic scenario of neurodegenerative disorders.

LAB MEMBERS

Research Head: Rodrigo Pacheco

Doctoral students: Javier Campos • Zulmary Manjarres

Research Assistants: Valentina Ugalde • María Alexandra Espinoza • Ornella Chovar

Post-doctoral Fellows: José Manuel Jimenez

Research Associates: Carolina Prado

FORMER LAB MEMBERS

Hugo González (former PhD Student and post-doctoral fellow 2009-2014)
Postdoctoral fellow at UCSF, United States of America.

Francisco Contreras (former PhD Student and post-doctoral fellow 2010-2017)
Technical Director at Dolphin Medical, Chile.

María Gabriela Colmenares (former post-doc 2017)
Post-doctoral fellow at Mayo Clinic, United States of America.

Pía Vidal (former post-doc 2018-2019)
Assistant Professor at Universidad Católica de la Santísima Concepción, Chile

Daniela Elgueta (former PhD Student and post-doctoral fellow 2014-2020)
Post-doctoral fellow at Universidad Mayor, Chile.

Andro Montoya (former PhD Student 2011-2019)
Professor at Universidad de las Américas, Chile.

Francisco Osorio-Barrios (former undergraduated student and MSc Student 2013-2016)
PhD Student at Max Plank Institute, Germany.

Nicole Rivera (former MSc Student 2016-2018)
Technical assistant at Laboratorio de Química Clínica Especializada Limitada, Chile.

Pablo Díaz (Undergraduated Student 2009-2010)
Scientific advisor at Instituto de salud pública, Chile.

Dafne Franz (Undergraduated Student 2010-2012)
Postdoctoral fellow at University College London, United Kingdom.

Glenda Fuentealba (Undergraduated Student 2011-2013)
Technical assistant at Merken Biotech, Chile

Catalina Valeria (Undergraduated Student 2013-2014)
Obstetrics student at Universidad de Concepción, Chile.

COLLABORATIONS

National Collaborations:
• Dr. Luis Michea (University of Chile)
• Dr. María Rosa Bono (University of Chile)
• Dr. Jimmy Stehberg (University Andrés Bello)
• Dr. Andrea Soza and Dr. Patricia Burgos (University San Sebastián)
• Dr. Isabel Yuseff (Pontificia Universidad Católica de Chile)
• Dr. Margarita Calvo (Pontificia Universidad Católica de Chile)
• Dr. Alberto J. Martin (University Mayor)
• Dr. Felipe Court (University Mayor)
• Dr. Alvaro Lladser (Fundación Ciencia & Vida)
• Dr. Tomás Pérez-Acle (Fundación Ciencia & Vida)
• Dr. Mario Rosemblatt (Fundación Ciencia & Vida)
• Dr. Alejandra Loyola (Fundación Ciencia & Vida)

International Collaborations:
• Dr Rafael Franco and Dr Gemma Navarro (University of Barcelona)
• Dr. Marco Cosentino (University of Insubria)
• Dr. Pablo Vargas (Institute Curie)

SELECTED PUBLICATIONS

  • Ugalde V., Contreras F., Prado C., Chovar O., Espinoza A., Pacheco R. Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation. Mucosal Immunol. In press. doi: 10.1038/s41385-020-00354-7 (2020). | | ABSTRACT
  • Campos J., Pacheco R. Involvement of Dopaminergic Signaling in the Cross-Talk Between the Renin-Angiotensin System and Inflammation. Semin Immunopathol. 42(6):681-696. doi: 10.1007/s00281-020-00819-8 (2020). | | ABSTRACT
  • Vidal P., Pacheco R. The Cross-Talk Between the Dopaminergic and the Immune System Involved in Schizophrenia. Front Pharmacol. 11: 394. doi: 10.3389/fphar.2020.00394 (2020). | PDF | ABSTRACT
  • Vidal P., Pacheco R. Targeting the dopaminergic system in autoimmunity. J Neuroimmune Pharmacol. 15(1): 57-73. doi: 10.1007/s11481-019-09834-5 (2020). | PDF | ABSTRACT
  • Comi C, Cosentino M, Pacheco R. Editorial: Peripheral Immunity in Parkinson's Disease: Emerging Role and Novel Target for Therapeutics. Front Neurol. 10(1): 1080. doi: 10.3389/fneur.2019.01080 (2019) | PDF | ABSTRACT
  • Prado C, Ugalde V, González H, Figueroa A, López E, Lladser A, Pacheco R. STAT3 activation in combination with NF-kappaB inhibition induce tolerogenic dendritic cells with high therapeutic potential to attenuate collagen-induced arthritis. J Immunol Res. 1982570. doi: /10.1155/2019/1982570 (2019). | PDF | ABSTRACT
  • Pacheco R. Cross-talk between T-cells and gut-microbiota in neurodegenerative disorders. Neural Regen Res. 14(12):2091-2092. doi: 10.4103/1673-5374.262582 (2019). | PDF | ABSTRACT
  • Araos P, Prado C, Lozano M, Figueroa S, Espinoza A, Berger T, Mak TW, Jaisser F, Pacheco R, Michea L, Amador CA. Dendritic cells are crucial for cardiovascular remodeling and modulate Neutrophil Gelatinase-Associated Lipocalin (NGAL) expression upon mineralocorticoid receptor activation. J Hypertens. 37(7): 1482-1492. doi: 10.1097/HJH.0000000000002067 (2019). | PDF | ABSTRACT
  • Campos-Acuña J, Elgueta D, Pacheco R. T-cell-driven inflammation as a mediator of the gut-brain axis involved in Parkinson’s disease. Front Immunol. 10(1): 239. doi: 10.3389/fimmu.2019.00239 (2019). | PDF | ABSTRACT
  • Medel B, Costoya C, Fernandez D, Pereda C, Lladser A, Sauma D, Pacheco R, Iwawaki T, Salazar-Onfray F, Osorio F. IRE1α activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T cell Priming. Front Immunol. 9(1): 3050. doi: 10.3389/fimmu.2018.03050 (2019). | PDF | ABSTRACT
  • Pardo-Esté C, Hidalgo A.A., Aguirre C., Briones A.C., Cabezas C.E., Castro-Severyn J., Fuentes J.A., Opazo C.M., Riedel C.A., Otero C., Pacheco R., Valvano M.A., Saavedra C.P. The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimurium. PLoS One. 13(9):e0203497. doi: 10.1371/journal.pone.0203497 (2018). | PDF | ABSTRACT
  • Osorio-Barrios F., Prado C., Contreras F., Pacheco R. Dopamine receptor D5 signalling plays a dual role in experimental autoimmune encephalomyelitis potentiating Th17-mediated immunity and favouring suppressive activity of regulatory T-cells. Front Cell Neurosci. 12(1): 192. doi: 10.3389/fncel.2018.00192 (2018). | PDF | ABSTRACT
  • Prado C., Iruretagoyena M., Burgos P.I., Pacheco R. Tobacco promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients. Rev Med Chil. 146(2): 150-159. doi: 10.4067/s0034-98872018000200150 (2018). | PDF | ABSTRACT
  • Prado C., Gaiazzi M., González H., Ugalde V., Figueroa A., Osorio-Barrios F., López E., Lladser A., Rasini E., Marino F., Zaffaroni M., Cosentino M., Pacheco R. Dopaminergic stimulation of myeloid antigen-presenting cells attenuates STAT3-activation favouring the development of experimental autoimmune encephalomyelitis. Front. Immunol. 9:571. doi: 10.3389/fimmu.2018.00571(2018) | | ABSTRACT
  • Hevia D., Araos P., Prado C., Fuentes-Luppichini E,, Rojas M., Alzamora R., Cifuentes-Araneda F., Gonzalez A. A., Amador C. A., Pacheco R., Michea L. Myeloid CD11c+ antigen-presenting cells ablation prevents hypertension in response to angiotensin II plus high-salt diet. Hypertension 71(4):709-718. doi: 10.1161/HYPERTENSIONAHA.117.10145 (2018) | | ABSTRACT
  • Pardo E., Cárcamo C., Uribe-San Martín R., Ciampi E., Segovia-Miranda F., Curkovic C., Montecino F., Holmes C., Tichauer J. E., Acuña E., Osorio-Barrios F., Castro M., Cortes P., Oyanadel C., Valenzuela D., Pacheco R., Naves R., Soza A., González A. Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis. PLoS ONE 12(6):e0177472 (2017) | | ABSTRACT
  • Doñas C., Carrasco M., Fritz M., Prado C., Tejón G., Osorio-Barrios F., Manríquez V., Pacheco R., Reyes P., Bono M. R., Loyola A., Rosemblatt M. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on dendritic cells. J. Autoimmun. 75:105-117. doi: 10.1016/j.jaut.2016.07.011 (2016). | | ABSTRACT
  • Elgueta D., Aymerich M. S., Contreras F., Montoya A., Celorrio M., Rojo-Bustamante E., Riquelme E., González H., Vásquez M., Franco R., Pacheco R. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease. Neuropharmacology 113:110-123 (2017) | | ABSTRACT
  • Figueroa C., Gálvez-Cancino F., Oyarce C., Contreras F., Prado C., Valeria C., Cruz S., Lladser A., Pacheco R. Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity. J. Neuroimmunol. 303:99-107 (2017) | | ABSTRACT
  • Pacheco R. Targeting dopamine receptor D3 signalling in inflammation. Oncotarget 8(5):7224-7225 (2017) | | ABSTRACT
  • Contreras F., Prado C., González H., Franz D., Osorio-Barrios F., Osorio F., Ugalde V., Lopez E., Elgueta D., Figueroa A., Lladser A., Pacheco R. Dopamine receptor D3 signaling on CD4+ T cells favors Th1- and Th17-mediated immunity. J. Immunol. 196(10):4143 (2016) | | ABSTRACT
  • Fernández D., Flores-Santibáñez F., Neira J., Osorio F., Tejón G., Núñez S., Hidalgo Y., Fuenzalida M. J., Meza D., Ureta G., Lladser A., Pacheco R., Acuña-Castillo C., Guixé V., Quintana F. J., Bono M. R., Rosemblatt M., Sauma D. Purinergic signaling as a regulator of Th17 cell plasticity. PloS ONE 11(6): e0157889 (2016) | | ABSTRACT
  • Moraga-Amaro R., González H., Ugalde V., Donoso-Ramos J. P., Quintana-Donoso D., Lara M., Morales B., Rojas P., Pacheco R., Stehberg J. Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory. Neuropharmacol. 103: 222-235 (2016) | | ABSTRACT
  • Oliva H., Pacheco R., Rodríguez-García M., Naranjo-Gómez M., Climent N., Martínez-Navio J. M., Gil C., Plana M., García F., Miró J. M., Franco R., Borras F., Navaratnam N., Gatell J. M., Gallart T. Increased expression with differential subcellular location of cytidine deaminase APOBEC3G in human CD4+ T-cell activation and dendritic cell maturation. Immunol. Cell Biol. doi: 10.1038/icb.2016.28 (2016) | | ABSTRACT
  • González H., Contreras F., Pacheco R. Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells. J. Neuroimmune Pharmacol. 10(4): 561-575 (2015) | | ABSTRACT
  • Franz D., Contreras F., González H., Prado C., Elgueta D., Figueroa C., Pacheco R. Dopamine receptors D3 and D5 regulate CD4 +T-cell activation and differentiation by modulating ERK activation and cAMP production. J. Neuroimmunol. 284: 18-29 (2015) | | ABSTRACT
  • González H., Pacheco R. T-cell mediated regulation of neuroinflammation involved in neurodegenerative diseases. J. Neuroinflammation 11(1): 201 (2014) | | ABSTRACT
  • Fernández-Suárez D., Celorrio M., Riezu-Boj J. I., Pacheco R., González H., Hillard C. J., Franco R., Aymerich M. S. Neuroprotective effect of the monoacylglycerol lipase inhibitor JZL184 in a chronic MPTP mouse model. Neurobiol. Aging 35(11): 2603-2616 (2014) | | ABSTRACT
  • Moraga-Amaro R., González H., Pacheco R., Stehberg J. Dopamine receptor D3 deficiency results in chronic depression and anxiety. Behav. Brain Res. 274(1): 186-193 (2014) | | ABSTRACT
  • González H., Elgueta D., Montoya A., Pacheco R. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J. Neuroimmunol. 274(1-2): 1-13 (2014)| | | ABSTRACT
  • Pacheco R., Contreras F. and Zouali M. The dopaminergic system in autoimmune diseases. Frontiers in Immunology. 5: 117. (2014) | PDF | ABSTRACT
  • González H., Contreras F., Prado C., Elgueta D., Franz D., Bernales S. and Pacheco R. Dopamine receptor D3 expressed on CD4+ T-cells favours neurodegeneration of dopaminergic neurons during Parkinson's disease. Journal of Immunology. 190(10):5048-5056. (2013) | PDF | ABSTRACT
  • Prado C., Bernales S. and Pacheco R. Modulation of T-cell mediated immunity by dopamine receptor D5. Endocrine, Metabolic & Immune Disorders-Drug Target. 13(2):184-194. (2013) | PDF | ABSTRACT
  • Prado C., Contreras F., González H., Díaz P., Elgueta D., Barrientos M., Herrada A. A., Lladser À., Bernales S. and Pacheco R. Immunity on Dendritic Cells Potentiates Th17-Mediated Stimulation of Dopamine Receptor D5 Expressed. J. Immunol. 188, 3062-3070 (2012) | PDF | ABSTRACT
  • Martinez-Navio J. M., Casanova V., Pacheco R., Naval-Macabuhay I., Climent N., Garcia F., Gatell J. M., Mallol J., Gallart T., Lluis C. and Franco R. Adenosine deaminase potentiates the generation of effector, memory and regulatory CD4+ T-cells. J. Leukoc. Biol. 89 (1): 127-136 (2011) | PDF | ABSTRACT
  • Pacheco R., Prado C. E., Barrientos M. J., Bernales S. Role of dopamine in the physiology of T-cells and dendritic cells. J. Neuroimmunol. 216 (1-2): 8-19 (2009) | PDF | ABSTRACT
  • Carreño L. J., Pacheco R., Gutierrez M. A., Jacobelli S., Kalergis A. M. Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fcᵞ receptors and costimulatory molecules on dendritic cells. Immunology 128 (3): 334-341 (2009) | PDF | ABSTRACT
  • Martinez-Navio J. M., Climent N., Pacheco R., Garcia F., Plana M., Nomdedeu M., Oliva H., Rovira C., Miralles L., Gatell J. M., Gallart T., Mallol J., Lluis C. and Franco R. Immunological Dysfunction in HIV-1-Infected Individuals caused by Impairment of adenosine deaminase-induced costimulation of T-Cell activation. Immunology 128 (3): 393-404 (2009) | PDF | ABSTRACT
  • Herrada A. A., Contreras F. J., Tobar J. A., Pacheco R. and Kalergis A. M. Immune complex-induced enhancement of bacterial antigen presentation requires FcУ Receptor III expression on dendritic cells. PNAS 104 (33): 13402-13407 (2007) | PDF | ABSTRACT
  • Franco R., Pacheco R., Lluis C., Ahern G. P. and O’Connell P. J. The emergence of neurotransmitters as immune modulators. Trends Immunol. 28 (9): 400-407 (2007) | PDF | ABSTRACT
  • Pacheco R., Gallart T., Lluis C. and Franco R. Role of glutamate on T-cell mediated immunity. J. Neuroimmunol. 185 (1-2): 09-19 (2007) | PDF | ABSTRACT