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Our work focused on a leaderless IL\u20101\u03b2 protein secretion from human macrophage in response to\n                    <jats:italic>Acanthamoeba castellanii<\/jats:italic>\n                    components,\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    culture supernatant (CS) and cell lysate (CL), as well as its association with macrophage autophagy. Phorbol 12\u2010myristate 13\u2010acetate (PMA)\u2013induced THP\u20101 macrophages were treated with\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    components of pathogenic (ATCC50739) and nonpathogenic (ATCC30010) strains in vitro. The data showed that\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    treatment resulted in low IL\u20101\u03b2 secretion from macrophages. In addition,\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    CL of both strains was able to upregulate autophagy\u2010related (Atg) protein 8, an autophagy marker, whereas\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    CS downregulated Atg8 expression. We further manipulated autophagy and found that autophagy induction by starvation diminished IL\u20101\u03b2 secretion while autophagy inhibition by 3\u2010methyladenine (3MA) increased IL\u20101\u03b2 secretion. Interestingly, in the presence of\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    components either under starvation or 3MA treatment, IL\u20101\u03b2 secretion was significantly reduced. Transcriptional expression of other ATG genes, i.e., ATG6, ATG7, and ATG5, were investigated and showed that their mRNA expression was maintained at the basal level under\n                    <jats:italic>A. castellanii<\/jats:italic>\n                    CS or CL treatment. Inflammasome\u2010related genes, NLRP3 and CASPASE1, were upregulated following\n                    <jats:italic>A. castellanii<\/jats:italic>\n                    50739 CS treatment but not in\n                    <jats:italic>A. castellanii<\/jats:italic>\n                    50739 CL\u2010treated condition. However, both conditions were able to increase IL\u20101\u03b2 mRNA expression. TEM micrographs revealed that 3MA treatment induced the formation of large vacuoles and accumulation of autophagosome at the edge of THP\u20101 macrophages. However, the number and size of their structures were declined in the presence of\n                    <jats:italic>A. castellanii<\/jats:italic>\n                    50739 CS with 3MA. Furthermore, immunofluorescence staining demonstrated the association between Atg8\/LC3 and IL\u20101\u03b2 expression, where downregulation of Atg8 by\n                    <jats:italic>A. castellanii<\/jats:italic>\n                    50739 CS led to the upregulation of IL\u20101\u03b2. Altogether, the data indicate that\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    can manipulate macrophage autophagy, thereby controlling low IL\u20101\u03b2 secretion. The expression of autophagy\u2010 and inflammasome\u2010related genes also indicates multiple mechanisms in IL\u20101\u03b2 secretion in response to\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    components. However, further characterization of Atg proteins and investigations into other intracellular pathways or defense mechanisms are needed to fully understand the unconventional secretion of IL\u20101\u03b2 in macrophages. This knowledge could eventually lead to the development of innovative therapeutic strategies against\n                    <jats:italic>Acanthamoeba<\/jats:italic>\n                    infection by modulating autophagy or macrophage responses.\n                  <\/jats:p>","DOI":"10.1155\/sci5\/3430892","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T02:05:11Z","timestamp":1741831511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Acanthamoeba castellanii<\/i>\n                    \u2013Mediated Reduction of Interleukin\u20101\u03b2 Secretion and Its Association With Macrophage Autophagy"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-1594","authenticated-orcid":false,"given":"Rachasak","family":"Boonhok","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-3472","authenticated-orcid":false,"given":"Wilaiwan","family":"Senghoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-5521","authenticated-orcid":false,"given":"Suthinee","family":"Sangkanu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-892X","authenticated-orcid":false,"given":"Chooi Ling","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-4124","authenticated-orcid":false,"given":"Matsayapan","family":"Pudla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-7869","authenticated-orcid":false,"given":"Maria de Lourdes","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-7788","authenticated-orcid":false,"given":"Polrat","family":"Wilairatana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-776X","authenticated-orcid":false,"given":"Tooba","family":"Mahboob","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-8923","authenticated-orcid":false,"given":"Md. 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