{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T03:29:22Z","timestamp":1775186962894,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T00:00:00Z","timestamp":1693699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2018R1D1A1B07048097"],"award-info":[{"award-number":["NRF-2018R1D1A1B07048097"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["NRF-2021R1A2C1091855"],"award-info":[{"award-number":["NRF-2021R1A2C1091855"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) of protozoan parasites have diverse biological functions that are essential for parasite survival and host\u2013parasite interactions. In this study, we characterized the functional properties of EVs from Naegleria fowleri, a pathogenic amoeba that causes a fatal brain infection called primary amoebic meningoencephalitis (PAM). N. fowleri EVs (NfEVs) have been shown to be internalized by host cells such as C6 glial cells and BV-2 microglial cells without causing direct cell death, indicating their potential roles in modulating host cell functions. NfEVs induced increased expression of proinflammatory cytokines and chemokines such as TNF-\u03b1, IL-1\u03b1, IL-1\u03b2, IL-6, IL-17, IFN-\u03b3, MIP-1\u03b1, and MIP-2 in BV-2 microglial cells; these increases were initiated via MyD88-dependent TLR-2\/TLR-4. The production levels of proinflammatory cytokines and chemokines in NfEVs-stimulated BV-2 microglial cells were effectively downregulated by inhibitors of MAPK, NF-\u03baB, or JAK-STAT. Phosphorylation levels of JNK, p38, ERK, p65, JAK-1, and STAT3 were increased in NfEVs-stimulated BV-2 microglial cells but were effectively suppressed by each corresponding inhibitor. These results suggest that NfEVs could induce proinflammatory immune responses in BV-2 microglial cells via the NF-\u03baB-dependent MAPK and JAK-STAT signaling pathways. Taken together, these findings suggest that NfEVs are pathogenic factors involved in the contact-independent pathogenic mechanisms of N. fowleri by inducing proinflammatory immune responses in BV-2 microglial cells, further contributing to deleterious inflammation in infected foci by activating subsequent inflammation cascades in other brain cells.<\/jats:p>","DOI":"10.3390\/ijms241713623","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:14:50Z","timestamp":1693793690000},"page":"13623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Naegleria fowleri Extracellular Vesicles Induce Proinflammatory Immune Responses in BV-2 Microglial Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"H\u01b0\u01a1ng Giang","family":"L\u00ea","sequence":"first","affiliation":[{"name":"Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Mi","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tu\u1ea5n C\u01b0\u1eddng","family":"V\u00f5","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3041-5560","authenticated-orcid":false,"given":"Won Gi","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6734-1673","authenticated-orcid":false,"given":"Byoung-Kuk","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by extracellular vesicles: Where we are and where we need to go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. 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