Prior Trichinella spiralis infection protects against Schistosoma mansoni induced hepatic fibrosis

Asmaa M El-Kady; Sarah A Altwaim; Majed H Wakid; Alaa S Banjar; Khalil Mohammed; Mashael S Alfaifi; Hayam Elshazly; Wafa Abdullah I Al-Megrin; Eman Abdullah Alshehri; Eman Sayed; Hatem A Elshabrawy

doi:10.3389/fvets.2024.1443267

Prior Trichinella spiralis infection protects against Schistosoma mansoni induced hepatic fibrosis

Front Vet Sci. 2024 Oct 8:11:1443267. doi: 10.3389/fvets.2024.1443267. eCollection 2024.

Authors

Asmaa M El-Kady¹, Sarah A Altwaim^{2

3}, Majed H Wakid^{3

4}, Alaa S Banjar^{4

5}, Khalil Mohammed⁶, Mashael S Alfaifi⁶, Hayam Elshazly^{7

8}, Wafa Abdullah I Al-Megrin⁹, Eman Abdullah Alshehri¹⁰, Eman Sayed¹¹, Hatem A Elshabrawy¹²

Affiliations

¹ Department of Medical Parasitology, Faculty of Medicine, South Valley University, Qena, Egypt.
² Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Special Infectious Agents Unit, King Fahd Medical Research Center, Jeddah, Saudi Arabia.
⁴ Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Center of Innovation in Personalized Medicine (CIPM), King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Department of Epidemiology and Medical Statistics, Faculty of Public Health and Health Informatics, Umm Al-Qura University, Mecca, Saudi Arabia.
⁷ Department of Biology, Faculty of Sciences-Scientific Departments, Qassim University, Buraidah, Qassim, Saudi Arabia.
⁸ Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef, Egypt.
⁹ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
¹⁰ Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
¹¹ Department of Parasitology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt.
¹² Department of Molecular and Cellular Biology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX, United States.

Abstract

Background: Schistosomiasis affects approximately 250 million people worldwide, with 200,000 deaths annually. It has been documented that the granulomatous response to Schistosoma mansoni (S. mansoni) oviposition is the root cause of progressive liver fibrosis in chronic infection, in 20% of the patients, and can lead to liver cirrhosis and/or liver cancer. The influence of helminths coinfection on schistosomiasis-induced liver pathological alterations remains poorly understood. Therefore, in this study, we investigated the effect of Trichinella spiralis (T. spiralis) infection on S. mansoni-induced hepatic fibrosis.

Materials and methods: Thirty adult male Balb-c mice were divided into three groups. Group 1 was left uninfected; group 2 was infected with S. mansoni cercariae and group 3 was orally infected with T. spiralis larvae, then 28 days later, this group was infected with S. mansoni cercariae. All groups were sacrificed at the end of the 8^th week post infection with S. mansoni to evaluate the effect of pre-infection with T. spiralis on S. mansoni induced liver fibrosis was evaluated parasitologically (worm burden and egg count in tissues), biochemically (levels of alanine aminotransferase and aspartate aminotransferase), histopathologically (H&E and MT staining, and immunohistochemical staining for the expression of α-SMA, IL-6, IL-1β, IL-17, IL-23, TNF-α, and TGF-β).

Results: The results in the present study demonstrated marked protective effect of T. spiralis against S. mansoni induced liver pathology. We demonstrated that pre-infection with T. spirais caused marked reduction in the number of S. mansoni adult worms (3.17 ± 0.98 vs. 18 ± 2.16, P = 0.114) and egg count in both the intestine (207.2 ± 64.3 vs. 8,619.43 ± 727.52, P = 0.009) and liver tissues (279 ± 87.2 vs. 7,916.86 ± 771.34; P = 0.014). Consistently, we found significant reductions in both number (3.4 ± 1.1 vs. 11.8.3 ± 1.22; P = 0.007) and size (84 ± 11 vs. 294.3 ± 16.22; P = 0.001) of the hepatic granulomas in mice pre-infected with T. spiralis larvae compared to those infected with only S. mansoni. Furthermore, pre- infection with T. spiralis markedly reduced S. mansoni- induced hepatic fibrosis, as evidenced by decreased collagen deposition, low expression of α-SMA, and significantly reduced levels of IL-17, IL-1B, IL-6, TGF-B, IL-23, and TNF-α compared to mice infected with S. mansoni only.

Conclusions: Our data show that pre-infection with T. spiralis effectively protected mice from severe schistosomiasis and liver fibrosis. We believe that our findings support the potential utility of helminths for the preventing and ameliorating severe pathological alterations induced by schistosomiasis.

Keywords: Schistosoma mansoni; Trichinella spiralis; fibrosis markers; hepatic fibrosis; murine model.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors extend their acknowledgment to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R39), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia and Researchers Supporting Project number (RSPD2024R859), King Saud University, Riyadh, Saudi Arabia.