The effective defense against infections requires the ability to mount different types of specific immune responses against the invading agent that are initiated and maintained by different classes of effector CD4 + and CD8 + T cells (Th1, Th2, or Th17). The magnitude of the immune response (in excess or in detriment) is controlled by regulatory T cells (Tregs). The optimal balance between the different types of effector and regulatory cells is orchestrated by antigen presenting cells (APCs), dendritic cells (DCs) and macrophages (Mo), which are responsible for detecting danger signals, activating defense or tissue repair mechanisms, and participate in the activation and instruction of T cells. APCs participate in the differentiation of T cells by secreting cytokines, expressing appropriate TCR ligands and costimulatory molecules, and expressing enzymes involved in the production or catabolism of mediators toxic or essential for T cells. The type of collaboration to be provided to T cells will depend on the type of activation these cells have undergone when surveying the microenvironment in which they develop. In this sense, APCs are capable of detecting and activating both by endogenous or exogenous stimuli generated by tissue injury or infection and by signals produced by cells of the adaptive immune system.
Thus, depending on their activation state, APCs can be subdivided into three large groups: a) pro-inflammatory, "classically activated" or "microbicidal" APCs; b) anti-inflammatory, "alternatively activated" or "tissue repairing" APCs and c) "regulatory" APCs that participate in the development of Th2 cells and Treg cells. Both innate and adaptive immune system signals can modify the physiology of APCs allowing them to participate in various homeostatic processes such as tissue remodeling and repair and defense against infection. However, each of these modifications must be properly regulated in order to avoid harmful consequences.
In our laboratory we study the modulation of APC activity in different physiological and pathological conditions. As a physiological situation, we have studied the regulation of DC activity and its participation in the polarization of the immune response during pregnancy. As a pathological situation, we study the modulation of APC function during experimental infection with the Trypanosoma cruzi and Fasciola hepatic parasites. This last topic is carried out in close collaboration with the group led by Dra. Laura Cervi.
Specifically, the projects currently underway are:
• Role of the aryl hydrocarbon receptor (AhR) in the regulation of the protective immune response and immunopathology during the infection with Trypanosoma cruzi.
• Infection with Trypanosoma cruzi: role of the Wnt signaling pathway in the control of parasite replication and the regulation of the inflammatory immune response.
• Deciphering the dialogue between cardiomyocytes and macrophages in the cardiomyopathy associated with Trypanosoma cruzi infection: Role of Wnt proteins.
• Impact of the Wnt signaling pathways in the regulation of the transcriptional, metabolic and functional profile of macrophages infected with Trypanosoma cruzi.
- Volpini, Ximena, Ambrosio, Laura, Brajin, Maria Agustina, Brugo, Maria Belen, Aoki, María del Pilar, Rivarola, Hector Walter, Alfonso, Fernando, Fozzatti, Laura, Cervi, Laura, Motran, Claudia Cristina."Wnt Signaling Plays a Key Role in the Regulation of the Immune Response and Cardiac Damage During Trypanosoma cruzi Infection. ACS Infectious disease, 2021, DOI: 10.1021/acsinfecdis.0c00590 in press.
- Cerbán FM, Stempin CC, Volpini X, Carrera Silva EA, Gea S, Motran CC. Signaling pathways that regulate Trypanosoma cruzi infection and immune response. Biochim Biophys Acta Mol Basis Dis. 2020 Jan 28;1866(5):165707. doi: 10.1016/j.bbadis.2020.165707.
- Laura Fernanda Ambrosio, Constanza Insfran, Ximena Volpini, Eva Acosta Rodriguez, Horacio Marcelo Serra, Francisco J. Quintana, Laura Cervi and Claudia Cristina Motrán. Role of Aryl Hydrocarbon Receptor (AhR) in the regulation of Immunity and Immunopathology During Trypanosoma cruzi Infection. Frontiers in Immunology. 2019, Mar 29;10:631. doi: 10.3389/fimmu.2019.00631.
- Ximena Volpini, Laura F. Ambrosio, Laura Fozzatti, Constanza Insfran, Cinthia C. Stempin, Laura Cervi and Claudia Cristina Motran. Trypanosoma cruzi Exploits Wnt Signaling Pathway to Promote Their Intracellular Replication in Macrophages. Frontiers in Immunology. 2018. 9:859. doi: 10.3389/fimmu.2018.00859.
- Motran, C.C, Silvane, L., Chiapello, L.S., Theumer, M.G., Ambrosio, L.F., Volpini, X., Celias, D.P., Cervi, L. Helminth Infections: Recognition and Modulation of the Immune Response by Innate Immune Cells. Front Immunol. 2018. 9:664. doi: 10.3389/fimmu.2018.00664.
- Carolina P. Knubel, Constanza Insfran, Fernando F. Martinez, Cintia Diaz Lujan, Ricardo E. Fretes, Martin G. Theumer, Laura Cervi, and Claudia C. Motran. 3-Hydroxykynurenine, a Tryptophan Metabolite Generated during the Infection, Is Active Against Trypanosoma cruzi. ACS Med. Chem. Lett., 2017, 8 (7), 757–761.
- Motran, C.C., Ambrosio, L., Volpini, X., Celias, D. Cervi, L. Dendritic Cells and Parasites: From Recognition and Activation to Immune Response Instruction. Seminars in Immunopathology. 2017 Feb; 39(2): 199-213.
- Martinez FF, Cervi L, Knubel CP, Panzetta-Dutari GM, Motran CC. The role of pregnancy-specific glycoprotein 1a (PSG1a) in regulating the innate and adaptive immune response. Am J Reprod Immunol. 2013 Apr;69(4):383-94.
- Martínez FF, Knubel CP, Sánchez MC, Cervi L, Motrán CC. Pregnancy-specific glycoprotein 1a activates dendritic cells to provide signals for Th17-, Th2-, and Treg-cell polarization. Eur J Immunol. 2012 Jun;42(6):1573-84.
- Knubel CP, Martínez FF, Acosta Rodríguez EV, Altamirano A, Rivarola HW, Diaz Luján C, Fretes RE, Cervi L, Motrán CC. 3-Hydroxy Kynurenine Treatment Controls T. cruzi Replication and the Inflammatory Pathology Preventing the Clinical Symptoms of Chronic Chagas Disease. PLoS One. 2011;6(10):e26550.
- Knubel, CP., Martinez, FF., Fretes, RE., Diaz Lujan, C., Theumer, MG., Cervi, L., Motran, CC. “Indoleamine 2,3 Dioxigenase (IDO) is critical for the host resistance against Trypanosoma cruzi.” The FASEB Journal. 2010, 24 (8): 2689-701. FI: 7.0