Innate immunity and inflammation
Several evidence indicate the importance of sensors innate immunity as Toll- like receptors (TLR) and inflammasomes in the signaling pathways of innate immunity not only against pathogens but also towards endogenous ligands generated by tissue damage in chronic processes. Infections, with particular interest in parasites, are cause of disease with significant impact on human health. A fault in the control mechanisms of the acute inflammatory response may affect the replication of the parasite Trypanosoma cruzi while an imbalance of it would lead to the development of severe inflammatory diseases.
Furthermore, obesity and associated metabolic diseases such as diabetes type II and cardiovascular diseases, represent a major cause of morbidity and mortality in society. Our project focuses on investigating the biology of myeloid suppressor cells during acute infection, its relationship with the induction of different types of cellular immune response and its relevance in the pathogenic mechanisms.
Furthermore, in an experimental model of chronic inflammation with metabolic disorders, an example of sterile inflammatory disease, we investigate how these sensors promote the development of inflammation and adaptive immunity and how the host-parasite interaction influence disease outcome.
Understanding the network between innate and adaptive immunity and the role of receptors during acute and chronic inflammation would allow the future development of new therapeutic strategies to improve the evolution of these infectious and inflammatory diseases.
Chronic Trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a diet-induced obesity model.
Cabalén ME, Cabral MF, Sanmarco LM, Andrada MC, Onofrio LI, Ponce NE, Aoki MP, Gea S, Cano RC. Oncotarget, 7(12):13400-15, 2016
Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders. Onofrio LI, Arocena AR, Paroli AF, Cabalén ME, Andrada MC, Cano RC, Gea S. PLoS Negl Trop Dis., 9(2):e0003464, 2015.
Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection. Arocena AR, Onofrio LI, Pellegrini AV, Carrera Silva AE, Paroli A, Cano RC, Aoki MP, Gea S. Eur J Immunol., 4(1):184-94, 2014
The role of Toll-like receptors and adaptive immunity in the development of protective or pathological immune response triggered by the Trypanosoma cruzi protozoan. Pellegrini A, Guiñazu N, Giordanengo L, Cano RC, Gea S. Future Microbiol., 6(12):1521-33, 2011.
Importance of TLR2 on hepatic immune and non-immune cells to attenuate the strong inflammatory liver response during Trypanosoma cruzi acute infection. Carrera-Silva EA, Guiñazu N, Pellegrini A, Cano RC, Arocena A, Aoki MP, Gea S. PLoS Negl.Trop Dis., 4(11):e86, 2010
Inducible Nitric Oxide Synthase and Arginase Expression in Heart Tissue during Acute Trypanosoma cruzi Infection in Mice: Arginase I Is Expressed in Infiltrating CD68(+) Macrophages. Cuervo H, Pineda MA, Aoki MP, Gea S, Fresno M, Gironès N.
Journal Infectious Disease 197(12):1772-82, 2008
Guiñazú N, Pellegrini A, Carrera-Silva EA, Aoki MP, Cabanillas AM, Gìronés N, Fresno M, Cano R, Gea S. Immunisation with a major Trypanosoma cruzi antigen promotes pro-inflammatory , nitric oxide production and increases TLR2 expression. Int J Parasitol.,37(11):1243-54, 2007
Cytokines and cell adhesion receptors in the regulation of immunity to Trypanosoma cruzi. Savino. W, Villa-Verde DMS, Mendes-da-Cruz AD, Silva-Monteiro E, Perez AR, Aoki M del P, Bottasso O, Guiñazú N, Silva-Barbosa SD, S Gea. Review.
Cytokines & Cell Growth Factors Reviews 18: 107-124, 2007
Aoki Mdel P, Cano RC, Pellegrini AV, Tanos T, Guiñazú NL, Coso OA, Gea S. Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein. Microbes Infect.,8(7):1723-31, 2006.
Giordanengo L, Guiñazú N, Stempin C, Fretes R, Cerbán F, Gea S. Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite. Eur J Immunol., 32(4):1003-11, 2002.