DNA methylation alterations caused by Leishmania infection may generate a microenvironment prone to tumour development

Abstract

DNA methylation is an epigenetic signature consisting of a methyl group at the 5’ cytosine of CpG dinucleotides. Modifications in DNA methylation pattern have been detected in cancer and infectious diseases and may be associated with gene expression changes. In cancer development DNA methylation aberrations are early events whereas in infectious diseases these epigenetic changes may be due to host/pathogen interaction. In particular, in leishmaniasis, a parasitic disease caused by the protozoan Leishmania, DNA methylation alterations have been detected in macrophages upon infection with Leishmania donovani and in skin lesions from patients with cutaneous leishmaniasis. Interestingly, different types of cancers, such as cutaneous malignant lesions, lymphoma and hepatocellular carcinoma, have been diagnosed in patients with a history of leishmaniasis. In fact, it is known that there exists an association between cancer and infectious diseases. Leishmania infection may increase susceptibility to develop cancer, but the mechanisms involved are not entirely clear. Considering these aspects, in this review we discuss the hypothesis that DNA methylation alterations induced by Leishmania may trigger tumorigenesis in long term infection since these epigenetic modifications may enhance and accumulate during chronic leishmaniasis.

Awakening the sleeping giant: Epstein–Barr virus reactivation by biological agents

“…During this study, it was observed that the reactivation of EBV occurred and displayed a high load of 3000 genome equivalents per ml (geq/ml), which was further reduced upon treatment with rituximab (Agteresch et al 2007 ). Several studies have shown that tumor generation occurs in Leishmania-infected individuals (Schwing et al 2019 , Ouattassi et al 2022 , Vega-Benedetti et al 2022 ). However, oncogenic EBV involvement remain unexplored in these tumors.…”

Global comparative transcriptomes uncover novel and population-specific gene expression in esophageal squamous cell carcinoma

“…Literature evidences support these plausible microbial infections in ESCC. For example (i) Infection of several species of Leishmania was observed with Squamous Cell Carcinoma in Brazil and Iran [52][53][54], and a long term infection of it suspected to induce DNA methylation alterations triggering tumorigenesis [52], (ii) CMV infection associated gastrointestinal tract lesion-esophagitis in a Japanese patient observed with a moderately differentiated squamous cell carcinoma [55] and reactivation of CMV infection among esophageal cancer patients undergoing chemotherapy in Japan [56], (iii) Cervical cancer patients in India [57] and colon cancer patients in India and Japan [58,59] found with Amoebiasis. Further, Entamoeba histolytica infects epithelial cells expressing EhADH adhesin together with the EhCP112 cysteine protease and damage epithelium [60].…”