Cytokine levels and inflammasome markers in tears and impression cytology from patients diagnosed with Acanthamoeba Keratitis

• Grant number: 24/04550-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 17, 2025
• End date: August 16, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Denise de Freitas
• Grantee: Larissa Fagundes Pinto
• Supervisor: Nicole Carnt
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of New South Wales (UNSW), Australia
• Associated to the scholarship: 22/07131-2 - In vitro and in vivo evaluation of inflammatory and humoral response in patients diagnosed with Acanthamoeba keratitis, BP.DR

Abstract

Acanthamoeba keratitis (AK) is a rare, high-morbidity infection that develops in the cornea, with the protozoan Acanthamoeba spp. as its etiological agent. Amoebae of this genus are widely distributed in nature, suggesting that humans will probably be exposed to this protozoan at some point in their lives, given that 50 to 100% of the population has serum antibodies specific to Acanthamoeba antigens. Some parts of the eye are considered immune privileged, and little is known about the immune responses that develop in AK. However, it has been observed in studies in the literature that secretory immunoglobulin A (sIgA) and some cytokines are important in controlling and preventing AK, and there is no report on the activation of inflammasomes by this protozoan. The outcomes of AK infection tend to be binary, lasting 3 months or less as a mild phenotype and others lasting over 9 months with severe inflammatory complications. For this reason, this study aims to evaluate in vivo the inflammatory responses developed during AK, including the production of sIgA; as well as investigate inflammasome activation parameters such as active IL-1², IL-18, caspase-1, gasdermin D, ASC, and NLRP3 in ocular infections caused by Acanthamoeba. This will help to better understand the evolution of the immune responses developed in the mild and severe outcomes of AK. Finally, we will molecularly characterize Acanthamoeba spp. clinical isolates obtained from patients diagnosed with AK and recruited for this study, as these may also contribute to severity.