Taenia solium excretory secretory proteins (ESPs) suppresses TLR4/AKT mediated ROS formation in human macrophages via hsa-miR-125.

Background: Helminth infections are a global health menace affecting 24% of the world population. They continue to increase global disease burden as their unclear pathology imposes serious challenges to patient management. Neurocysticercosis is classified as neglected tropical disease and is caused by larvae of helminthic cestode Taenia solium. The larvae infect humans and localize in central nervous system and cause NCC; a leading etiological agent of acquired epilepsy in the developing world. The parasite has an intricate antigenic make-up and causes active immune suppression in the residing host. It communicates with the host via its secretome which is complex mixture of proteins also called excretory secretory products (ESPs). Understanding the ESPs interaction with host can identify therapeutic intervention hot spots. In our research, we studied the effect of T. solium ESPs on human macrophages and investigated the post-translation switch involved in its immunopathogenesis. Methodology: T. solium cysts were cultured in vitro to get ESPs and used for treating human macrophages. These macrophages were studied for cellular signaling and miR expression and quantification at transcript and protein level. Conclusion: We found that T. solium cyst ESPs treatment to human macrophages leads to activation of Th2 immune response. A complex cytokine expression by macrophages was also observed with both Th1 and Th2 cytokines in milieu. But, at the same time ESPs modulated the macrophage function by altering the host miR expression as seen with altered ROS activity, apoptosis and phagocytosis. This leads to activated yet compromised functional macrophages, which provides a niche to support parasite survival. Thus T. solium secretome induces Th2 phenomenon in macrophages which may promote parasite's survival and delay their recognition by host immune system. Author summary: This article discusses the research conducted on the effect of Taenia solium excretory secretory proteins (ESPs) on human macrophages and its role in the immunopathogenesis of Neurocysticercosis (NCC). NCC is a neglected tropical disease caused by larvae of T. solium, which infect humans and localizes in the central nervous system. The larvae cause NCC, a leading cause of acquired epilepsy in the developing world. The study found that T. solium ESPs induce a Th2 immune response in macrophages, which may promote parasite survival and delay their recognition by the host immune system. The research further showed that ESPs modulate macrophage function by altering host miR expression, leading to activated yet compromised functionality that provides a niche for parasite survival. This study provides insights into the interaction of ESPs with the host, revealing therapeutic intervention hot spots to manage NCC and other helminthic infections. In the absence of suitable animal model for NCC, our study elucidates important and novel finding of parasite mediated suppression of host immune system. [ABSTRACT FROM AUTHOR]