Investigating the relationship between lung cancer and the infection with the parasite Toxoplasma gondii

Tarabulsi, M 2020, Investigating the relationship between lung cancer and the infection with the parasite Toxoplasma gondii , PhD thesis, University of Salford.

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Abstract

Toxoplasma gondii is an obligate intracellular organism that has a worldwide distribution and is highly prevalent among animals and humans. Although usually asymptomatic, it can cause serious diseases in immunocompromised individuals such as pneumonia, ocular toxoplasmosis and abortions. Many studies have investigated T. gondii among cancer patients. However, none have addressed the significance of the infection with this ubiquitous parasite among this group. We aimed to investigate the relationship between T. gondii infection and lung cancer. In a study done at Salford University (published, 2019), 72 lung samples from patients with lung cancer were investigated for T. gondii infection by nested PCR and immunohistochemistry (IHC), and it documented a striking 100% prevalence. We recruited ten lung samples via bronchoalveolar lavage from healthy individuals to be used as a control group for the lung cancer patients study. Samples were tested with nested PCR targeting five T. gondii specific markers (B1, SAG1, SAG2 3′, SAG2 5′ and SAG3) and only one sample was positive for T. gondii infection with all five markers and then was further confirmed by IHC. Statistical analysis revealed an extremely significant difference between the lung cancer patients and the non-cancerous control group (P<0.0001). Previous studies on mice and rats have demonstrated the involvement of iNOS and Arginase gene expression in T. gondii infection. Nothing is known about the role of iNOS and Arginase in human lung tissue infected with Toxoplasma. We have established and optimised an IHC protocol to detect iNOS and Arg-1 in lung cancer samples and established a double immunofluorescence (IF) protocol to colocalise and measure the degree of colocalisation of Arg-1/T. gondii and iNOS/T. gondii parasite in 51 lung cancer samples. IHC results revealed expression of Arg-1, iNOS and T. gondii in the bronchiolar epithelium, smooth muscle cells of blood vessels, alveolar macrophages and type I and II pneumocytes. IF results revealed, at the alveolar macrophage level, Pearson correlation coefficient (PCC) measurement documented a significantly higher Arg-1/T. gondii colocalisation than iNOS/T. gondii (P<0.00001), whereas at the T. gondii cysts, iNOS/T. gondii colocalisation was significantly higher than Arg-1/T. gondii(P<0.0031). On the other hand, at the level of the alveolar knobs, no differences were established in the colocalisation between Arg-1/T. gondii and iNOS/T. gondii (P=0.49). The difference in the level of expression between Arg-1 and iNOS suggest differences in the functions of these two markers in relation to T. gondii infection.

Item Type: Thesis (PhD)
Contributors: Hide, G (Supervisor)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Funders: Royal Embassy of Saudi Arabia Cultural Bureau London
Depositing User: muyassar Tarabulsi
Date Deposited: 07 Oct 2020 13:48
Last Modified: 07 Oct 2020 13:48
URI: http://usir.salford.ac.uk/id/eprint/58311

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