Research project

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.