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. 2022 Dec 22;11(1):18.
doi: 10.3390/biomedicines11010018.

Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus

Affiliations

Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus

Asmaa M El-Kady et al. Biomedicines. .

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 pathological 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.

Keywords: CD8; T1DM; Toxoplasma gondii; apoptosis; caspase-3; diabetes; insulin; islets of Langerhans.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Acute and chronic toxoplasmosis are associated with pancreatic pathological changes and reduced the numbers of islets of Langerhans. Pancreatic tissue sections of mice from different groups (n = 10/group) were stained with H & E stain and imaged at ×ばつ. (A) Representative image of pancreatic tissue sections of uninfected mice showing uniform rounded islets (black arrows) within pancreatic acini, with no inflammation, edema or necrosis. (B) Representative image of pancreatic tissue sections from the acute toxoplasmosis group showing enlarged islets of Langerhans with β cells (blue arrows), acute inflammatory infiltrate (black arrows), edema (arrow heads), and areas of necrosis (red arrows). (C) Representative image of pancreatic tissue sections from the chronic toxoplasmosis group showing significant reduction in size of the islets of Langerhans with β cells (blue arrows), mild infiltration by chronic inflammatory cells (black arrows) and areas showing fibrous-like material (red arrow). (D) Size of islets of Langerhans in uninfected, acute, and chronic toxoplasmosis mice groups. (E) Number of islets of Langerhans in uninfected, acute, and chronic toxoplasmosis mice groups/HPF. Data are expressed as mean ± SD (n = 10). Asterisks (*) indicate a statistically significant difference; p < 0.05 and "ns" indicates insignificant difference.
Figure 2
Figure 2
CD8+ T cells Infiltrated pancreatic islets of Langerhans of mice with chronic toxoplasmosis. Immunohistochemistry representative images of pancreatic tissue sections stained for CD8 showing absence of CD8+ T cell infiltration into islets of Langerhans of uninfected (A) and acute toxoplasmosis mice (B) but marked infiltration of CD8+ T cells into islets of Langerhans of chronic toxoplasmosis mice group (C).
Figure 3
Figure 3
Acute and chronic toxoplasmosis are associated with significantly lower number of insulin-producing-β cells of islets of Langerhans. Pancreatic tissue sections of mice from different groups (n = 10/group) were stained with anti-insulin antibody. (A) Representative image of pancreatic tissue sections of uninfected mice with strong insulin staining. (B) Representative image of pancreatic tissue sections of the acute toxoplasmosis group with smaller stained area of islets of Langerhans (fewer β cells) compared to uninfected group. (C) Representative image of pancreatic tissue sections of the chronic toxoplasmosis group with smaller stained area of islets of Langerhans (fewer β cells) compared to the acute toxoplasmosis group. (D) Number of β cells (insulin producing cells)/HPF in islets of Langerhans of different mice groups. Data are expressed as mean ± SD (n = 10). Asterisks (*) indicate statistically significant difference; p < 0.05.
Figure 4
Figure 4
Acute and chronic toxoplasmosis induced apoptotic cell death in pancreatic islets of Langerhans. Pancreatic tissue sections of mice from different groups (n = 10/group) were stained with anti-caspase-3 antibody. (A) Representative image of pancreatic tissue sections of uninfected mice showing weak caspase 3 signal. (B) Representative image of pancreatic tissue sections of the acute toxoplasmosis group showing stronger caspase-3 staining and higher number of caspase-3-postive cells (apoptotic cells). (C) Representative image of pancreatic tissue sections of the chronic toxoplasmosis group with high number of caspase-3-postive cells but less than the acute toxoplasmosis group. (D) Number of caspase-3 positive cells /HPF in islets of Langerhans of different mice groups. Data are expressed as mean ± SD (n = 10). Asterisks (*) indicate statistically significant difference; p < 0.05.

References

    1. Webster J.P., Dubey J.P. Toxoplasmosis of animals and humans. Parasites Vectors. 2010;3:112. doi: 10.1186/1756-3305年3月11日2. - DOI
    1. Dubey J.P. Advances in the life cycle of Toxoplasma gondii. Int. J. Parasitol. 1998;28:1019–1024. doi: 10.1016/S0020-7519(98)00023-X. - DOI - PubMed
    1. Sutterland A.L., Fond G., Kuin A., Koeter M.W.J., Lutter R., van Gool T., Yolken R., Szoke A., Leboyer M., de Haan L. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: Systematic review and meta-analysis. Acta Psychiatr. Scand. 2015;132:161–179. doi: 10.1111/acps.12423. - DOI - PubMed
    1. Ahmadpour E., Daryani A., Sharif M., Sarvi S., Aarabi M., Mizani A., Rahimi M.T., Shokri A. Toxoplasmosis in immunocompromised patients in Iran: A systematic review and meta-analysis. J. Infect. Dev. Ctries. 2014;8:1503–1510. doi: 10.3855/jidc.4796. - DOI - PubMed
    1. Galvan-Ramírez M.D.L.L., Troyo-Sanroman R., Roman S., Bernal-Redondo R., Castellanos J.L.V. Prevalence of Toxoplasma infection in Mexican newborns and children: A systematic review from 1954 to 2009. ISRN Pediatr. 2012;2012:501216. doi: 10.5402/2012/501216. - DOI - PMC - PubMed
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