Proteomic analysis of Toxoplasma gondii-associated paediatric anterior uveitis granulomas in rural areas of Egypt: insights into host-parasite proteomic crosstalk

Abstract Toxoplasma gondii ( T. gondii ) is a well-recognized cause of ocular parasitic infections. It shows a special predilection for the retina and posterior chamber of the eye. However, there has been a growing number of reports of Egyptian children from rural areas who present with granulomatous anterior segment lesions, which contrasts with the parasite’s typical posterior chamber preference. Ocular granuloma samples from 60 patients were screened for the presence of Toxoplasma gondii by quantitative PCR. Thirty samples were positive for the T. gondii B1 gene. Shotgun proteomic analysis of both T. gondii and human host proteins was performed to further explore the involvement of the Toxoplasma protein machinery in paediatric anterior uveitis. A total of 91 hydrophilic proteins associated with the Toxoplasma ME49 strain were identified across 10 ocular samples. The most detected proteins included Histone H4, Actin, Histone H2A, Histone 3, Calmodulin, Tubulin, Chaperonin, ATP synthase and Heat Shock Protein 90. Gene ontology (GO) analysis highlighted their functional relevance to invasion, virulence, replication, growth, and survival of active T. gondii tachyzoite stages. As for the host proteins, a total of 41 hydrophilic peptides were identified across the samples. The most abundant proteins detected were actin, albumin, fibrinogen beta chain, vimentin, histones H2B and H4, neutrophil defensin, and β globin. GO analysis revealed the allocation of the detected proteins to several biological processes such as active immune system processes, stress defence, and wound healing. These findings highlight the implication of T. gondii in the development of serious anterior segment affection in children. Exploration of the molecular mechanisms underlying the host-parasite interface can provide explanatory insights into the rather unusual localization of anterior segment granulomas associated with T. gondii infection. Also, attention should be paid to the role of environmental transmission and its impact of the routes of entry of this parasite into the immune-privileged ocular environment.