Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-021-06663-9 REVIEW Helminth protection against type‑1 diabetes: an insight into immunomodulatory efect of helminth‑induced infection Muhammad Adnan Sabir Mughal 1  · Muhammad Kasib Khan 1  · Zaheer Abbas 1  · Rao Zahid Abbas 2  · Hammad ur Rehman Bajwa 1  · Abdullah Khalid Chatha 1  · Muhammad Imran 4  · Zia ud Din Sindhu 3  · Asghar Abbas 5  · Arsalan Zafar 1  · Muhammad Nadeem 1 Received: 13 February 2021 / Accepted: 17 August 2021 © The Author(s), under exclusive licence to Springer Nature B.V. 2021 Abstract Helminths are the old dirty friends of humans from decades and may live undetected by the immune system for years in the tissues. They have evolved as good experts at subverting the immune system. Despite of their pathogenicity, they provide protection to their host against certain infammatory diseases such as diabetes by modulating the immune mechanisms. These parasites are extra-cellular and induce Th2 response which triggers the adaptive immune cells as well as innate immune cells to work synergistically allowing Tregs to work in a toll-like receptor-dependent manure. T-helper cells type-2 also secrete certain anti-infammatory cytokines including IL-4, IL-10, IL-13 and TGF-β which also provide protection against type-1 diabetes. Several helminths such as T. crassiceps, S. venezuelensis, flarial worms, Schistosoma spp. and T. spiralis have been reported to prevent diabetes in mouse models as well as in some clinical trials. Immunomodulatory talent of helminths is receiving greater attention to prevent diabetes. Herein, an attempt has been made to review and highlight the possible immuno-modulatory mechanisms by which helminths provide protection against diabetes. Moreover, this review also emphasizes on the use of helminth-derived molecules or synthetic derivatives of helminth-antigens in clinical trials to overcome rapidly growing autoimmune disorders including diabetes. Keywords Diabetes · Helminths · Autoimmunity · Immuno-modulation · Tregs Introduction Type-1 diabetes mellitus (T1DM) is an autoimmune disease in which host immune system attacks β-cells of pancreatic islet and cause tissue damage leading to impaired growth and function. Despite other causes of T1DM, β-cell dam- age because of autoimmunity has been reported in 70–90% of diabetic patients [1]. Diabetes is mainly classifed in to type-1 (Insulin dependent) and type-2 (non-insulin depend- ent) depending on age, β-cells damage, autoreactive anti- bodies presence and requirement of taking insulin from exogenous route. Diabetes, especially type-2 diabetes is now included in ten leading causes of death across the globe, which is a global health concern now a days [2]. Autoimmunity, a leading cause of diabetes, mainly occurs due to molecular mimicry and good hygienic conditions in which either the pathogens are unable to invade in the host body or they evade the host immune system by covering themselves with their host body antigens. As a result, in such condition, immune system lose its ability to distin- guish between the forging pathogen and the reactive T-cells start damaging its own body cells [3]. Though, the helminth infections are considered as a serious threat to the health of animals and humans across the globe their infection have shown to modulate such kind of immune mechanisms, * Muhammad Kasib Khan mkkhan@uaf.edu.pk 1 Epidemiology Laboratory, Department of Parasitology, University of Agriculture, Faisalabad 38000, Pakistan 2 Chemotherapy Laboratory, Department of Parasitology, University of Agriculture, Faisalabad 38000, Pakistan 3 Immuno-Parasitology Laboratory, Department of Parasitology, University of Agriculture, Faisalabad 38000, Pakistan 4 Molecular Parasitology Laboratory, Department of Parasitology, University of Agriculture, Faisalabad 38000, Pakistan 5 Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture, Multan, Pakistan