Citation: El-kady, A.M.; Alzahrani, A.M.; Elshazly, H.; Alshehri, E.A.; Wakid, M.H.; Gattan, H.S.; Al-Megrin, W.A.I.; Alfaifi, M.S.; Mohamed, K.; Alharbi, W.; et al. Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus. Biomedicines 2023, 11, 18. https://doi.org/10.3390/ biomedicines11010018 Academic Editors: Chrysi Koliaki and David G. Alleva Received: 2 November 2022 Revised: 7 December 2022 Accepted: 16 December 2022 Published: 22 December 2022 Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biomedicines Article Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus Asmaa M. El-kady 1, * , Amal M. Alzahrani 2 , Hayam Elshazly 3,4 , Eman Abdullah Alshehri 5 , Majed H. Wakid 6,7 , Hattan S. Gattan 6,7 , Wafa Abdullah I. Al-Megrin 8 , Mashael S. Alfaifi 9 , Khalil Mohamed 9 , Waheeb Alharbi 10 , Hatem A. Elshabrawy 11, * and Salwa S. Younis 12 1 Department of Medical Parasitology, Faculty of Medicine, South Valley University, Qena 83523, Egypt 2 Department of Biology, Faculty of Sciences & Arts in Almandaq, Al Baha University, Al Baha 65779, Saudi Arabia 3 Department of Biology, Faculty of Sciences-Scientific Departments, Qassim University, Buraidah 52571, Saudi Arabia 4 Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef 62521, Egypt 5 Department of Zoology, College of Science, King Saud University, Riyadh 11362, Saudi Arabia 6 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia 7 Special Infectious Agents Unit, King Fahd Medical Research Center, Jeddah 21589, Saudi Arabia 8 Departmentof Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia 9 Department of Epidemiology, Faculty of Public Health and Health Informatics, Umm Al-Qura University, Mecca 21961, Saudi Arabia 10 Department of Physiology, Faculty of Medicine, Umm Al-Qura University, Mecca 21961, Saudi Arabia 11 Department of Molecular and Cellular Biology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA 12 Departments of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt * Correspondence: asmaa.elkady@med.svu.edu.eg (A.M.E.-k.); hatem.elshabrawy@shsu.edu (H.A.E.) Abstract: Background: Previous studies have reported involvement of Toxoplasma gondii (T. gondii) infections in the pathogenesis of some autoimmune diseases, such as polymyositis, rheumatoid arthritis, autoimmune thyroiditis, and Crohn’s disease. However, data on the association between T. gondii infections and Type 1 diabetes mellitus (T1DM) are still controversial. Therefore, in the present study, we aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with T1DM. Materials and Methods: Three groups (10 mice each) of male Swiss Albino mice were used. One group of mice was left uninfected, whereas the second and third groups were infected with the acute virulent T. gondii RH strain and the chronic less virulent Me49 T. gondii strain, respectively. T. gondii-induced pancreatic patho- logical changes were evaluated by histopathological examination of pancreatic tissues. Moreover, the expression of insulin, levels of caspase-3, and the pancreatic infiltration of CD8 + T cells were evaluated using immunohistochemical staining. Results: Pancreatic tissues of T. gondii-infected animals showed significant pathological alterations and variable degrees of insulitis. Mice with acute toxoplasmosis exhibited marked enlargement and reduced numbers of islets of Langerhans. However, mice with chronic toxoplasmosis showed considerable reduction in size and number of islets of Langerhans. Moreover, insulin staining revealed significant reduction in β cell numbers, whereas caspase-3 staining showed induced apoptosis in islets of Langerhans of acute toxoplasmosis and chronic toxoplasmosis mice compared to uninfected mice. We detected infiltration of CD8 + T cells only in islets of Langerhans of mice with chronic toxoplasmosis. Conclusions: Acute and chronic toxoplasmosis mice displayed marked pancreatic pathological changes with reduced numbers of islets of Langerhans and insulin-producing-β cells. Since damage of β cells of islets of Langerhans is associated with the development of T1DM, our findings may support a link between T. gondii infections and the development of T1DM. Biomedicines 2023, 11, 18. https://doi.org/10.3390/biomedicines11010018 https://www.mdpi.com/journal/biomedicines