{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:21:30Z","timestamp":1787721690699,"version":"build-2784847793"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Micro- and nanoplastics (MNPs) are increasingly detected in human tissues, raising concerns regarding their potential impact on immune cell function. Monocytes are among the first immune cells to encounter and internalize these particles. However, the intracellular mechanisms triggered by MNPs exposure remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary human monocytes were exposed to 25\u00b5g\/mL of polystyrene (PS) MNPs ranging from 0.5 to 5 \u00b5m. Particle uptake and intracellular trafficking were investigated by transmission electron microscopy (TEM), while autophagy\u2013lysosomal and mitochondrial responses were assessed by Western blotting, quantitative PCR, ultrastructural analyses, and metabolic flux measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ultrastructural TEM analysis revealed that primary human monocytes internalize MNPs through phagocytosis, followed by phagosome maturation and fusion with lysosomes. At a molecular level, MNPs exposure is associated with marked remodeling of the autophagy\u2013lysosomal system, characterized by increased lysosomal abundance, elevated LC3-II\/I ratio, and accumulation of autophagy-related vesicular structures. Although p62 protein levels increased following exposure, no corresponding changes were observed at the transcriptional level for key autophagy-associated genes, suggesting predominantly post-transcriptional regulation of these pathways. MNPs exposure also altered mitochondrial organization, increasing mitochondrial number while reducing mitochondrial area. Consistently, expression of the mitophagy-related gene\n                      <jats:italic>PINK1<\/jats:italic>\n                      increased, particularly following exposure to 1\u00b5m particles. Functional analyses demonstrated size-dependent mitochondrial dysfunction, with 0.5\u00b5m and 1\u00b5m particles reducing mitochondrial respiratory capacity, whereas 5\u00b5m particles exerted minimal effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>To our knowledge, this study provides the first integrated, size-resolved characterization of MNPs uptake and intracellular responses in primary human monocytes, combining ultrastructural and biological evidence of phagocytic internalization, autophagy-lysosomal flux, mitochondrial homeostasis, and cellular bioenergetics within the same experimental framework. MNPs uptake was associated with concurrent alterations in the autophagy\u2013lysosomal axis, mitochondrial homeostasis, and cellular metabolism. Our findings further provide evidence that exposure to MNPs at 25\u00b5g\/mL affects key intracellular pathways involved in immune cell homeostasis. These results highlight a potential link between particle accumulation and cellular alterations, which may have implications for myeloid cell function and long-term health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1919477","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:48:06Z","timestamp":1787719686000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Micro- and nanoplastics remodel the autophagy-lysosomal axis and mitochondrial function in primary human monocytes"],"prefix":"10.3389","volume":"17","author":[{"given":"Stefania","family":"Pezzana","sequence":"first","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Broggiato","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Limanaqi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, \u201cL. 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Sacco\u201d Hospital, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"De Palma","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine (BioMeTra), University of Milan","place":["Milan, Italy"]},{"name":"Coordinated Research Center (CRC) Nano\/microplastics on Environments, Medicine, Ecology, Systems Interaction Studies \u2013 NEMESIS, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Bardini","sequence":"additional","affiliation":[{"name":"Tettamanti Center, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori","place":["Monza, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Fenizia","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan","place":["Milan, Italy"]},{"name":"Coordinated Research Center (CRC) Nano\/microplastics on Environments, Medicine, Ecology, Systems Interaction Studies \u2013 NEMESIS, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clema.2024.100220","article-title":"The world of plastic waste: A review","volume":"11","author":"Pilapitiya","year":"2024","journal-title":"Cleaner Mater"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1330396","article-title":"Microplastics exposure: Implications for human fertility, pregnancy and child health","volume":"14","author":"Zurub","year":"2023","journal-title":"Front Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.8b05297","article-title":"Are we speaking the same language? 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