{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T04:41:45Z","timestamp":1759380105953,"version":"build-2065373602"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Balamuthia mandrillaris infection in humans is rare and usually fatal. It is well established that <jats:italic>B. mandrillaris<\/jats:italic> can cause granulomatous amebic encephalitis (GAE). However, little is known about the factors that determine <jats:italic>B. mandrillaris<\/jats:italic> pathogenicity and its host-specific interactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we conducted a cohort study of five patients with <jats:italic>B. mandrillaris<\/jats:italic> GAE and analyzed immune pathway alterations, differentially expressed genes (DEGs), and changes in immune cell composition to delineate the immune response in this rare infectious disease using bulk transcriptome analysis. Notably, we conducted bulk and single-cell transcriptome sequencing on paired cerebrospinal fluid (CSF) and blood samples from a single patient across three distinct stages of infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of seven CSF specimens revealed a total of 5,177 DEGs as the infection progressed. The most enriched pathway among the upregulated DEGs was the \u201cPI3K-Akt signaling pathway\u201d. Moreover, its upstream pathways, the \u201cToll-like receptor (TLR) signaling pathway\u201d and \u201cJAK\/STAT signaling pathway\u201d, were also upregulated. Among these, <jats:italic>TLR2, TLR9<\/jats:italic>, and <jats:italic>IFN-I\/III<\/jats:italic>-related genes played a crucial role in activating these pathways. The single-cell transcriptome results served to validate these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Disscusion<\/jats:title><jats:p>Overall, our study aimed to elucidate the pathogenic mechanisms underlying <jats:italic>B. mandrillaris<\/jats:italic> GAE, providing novel insights into the associated immune responses.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1677014","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T04:21:17Z","timestamp":1759378877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bulk and single-cell transcriptome profiling reveals the dynamic immune response in granulomatous amebic encephalitis caused by Balamuthia mandrillaris: a cohort 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