Immunoregulation during cystic echinococcosis / hydatidosis: Impact on prognosis and biotherapies
Teacher. Chafia Touil-Boukoffa
Team: ” Cytokines and NO Synthases / Immunity and Pathogenesis ”
LBCM-FSB-USTHB
Cystic echinococcosis / hydatidosis is a parasitic disease transmitted to humans by the larval stage of a cestode: Echinococcus granulosus. It is characterized by a slow and silent evolution. The close and long-lasting adaptation of the parasite to its host involves the implementation of complex and progressive strategies, allowing it to avoid or counteract the mechanisms of rejection by the immune system. In addition, the variability and severity of the clinical expression of this parasitosis are associated with the duration and intensity of the infection but also with the antigenic plurality.
The diagnosis is delicate, often late with however a frequency of recidivism not negligible. The chemotherapies used are based on carbamates of benzimidazole as well as on isoquinoline derivatives. The data accumulated over the last decade by the different research teams concerning the elucidation of the mechanistic aspects of the host / Echinococcus granulosus ratio are in favor of the coexistence of the four sub-TCD4 + effector populations: Th1, Th2, Th17 and Treg (Touil-Boukoffa et al., 1997 and 1998, Rigano et al., 2004, Ait-Aissa et al., 2006, Mezioug and Touil -Boukoffa, 2009,2012, Amri et al, 2007, 2009, Siracusano et al., 2012). Several studies have reported the involvement of the Th1 pathway in protective immunity or resistance to infection. In contrast, the deviation to the Th2 and Treg pathways reflects susceptibility to disease (Amri et al, 2009). The work carried out by our team contributed to the demonstration of the implication of a strong NO production during the cystic echinococcosis. In this context, NOS2 competes with Arginase for the same L-Arginine substrate. The expression of NOS2 is regulated by cytokines from the four subpopulations (Amri et al, 2007, Amri and Touil-Boukoffa, 2015: Soufli et al, 2016, Khelifi et al, 2017). The understanding of the mechanisms of action and interactions in the context of cytokine network involvement has made it possible to situate immuno-pathological deviations (Amri et al 2015, Zeghir Boutedja et al, 2017) and to experimentally modulate the immune response towards the protective ways. It is with this in mind that our team evaluated in vitro and in vivo on an experimental model of secondary echinococcosis, the effect of the different cytokines markers of the 4 sub-populations TCD4 + (Th1, Th2, Th17 and Treg) and on the balance. NOS2 / Arginase).
The work done by our team will help to better understand this disease and put in place appropriate prophylactic measures. They should also open up new therapeutic perspectives for this pathology (Labsi et al, 2016, 2017). Finally, cystic echinococcosis constitutes a new and very promising parasitic model for understanding the pathophysiological mechanisms involved in many parasitic pathologies. Similarly, recent studies reported on helminthiases give them an additional advantage in understanding other pathophysiological mechanisms involved in chronic inflammatory diseases, allergy or autoimmune diseases, thanks to their immuno-regulatory power.
The research projects conducted by our team “Team Cytokine and NO Synthases / Immunity and Pathogeny” are organized around the following points:
a- The search for biomarkers of prognosis, patient follow-up and clinical diagnostic assistance.
b- The development of bio-therapeutic strategies on cytokines, anti-cytokines, pharmacological regulators of cytokine synthesis, biomolecules extracted from plants.
C- The use of helminthic helminthic components to inhibit the inflammatory processes of chronic inflammatory diseases (IBD) and autoimmune diseases through inhibition of TH1 / TH17 pathways.