{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:13:55Z","timestamp":1789496035593,"version":"build-2803163510"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Key Scientific Research Project of Higher Education Institutions in Henan Province","award":["25A310017"],"award-info":[{"award-number":["25A310017"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Trichinella spiralis<\/jats:italic>\n                      is a zoonotic parasitic nematode capable of infecting humans and animals, causing trichinellosis. It poses a critical threat to human health, livestock industry and food safety. The muscle larva of\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      is encased within a collagen capsule that is believed to protect it from host immunity. A strong macrophage-dominated inflammatory infiltrate accumulates around the capsule, yet how macrophages contribute to capsule formation remains unclear. Our objective was to investigate the effect of macrophage on collagen capsule formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>\n                      The results of immunofluorescence showed that S100A4\u2009\u207a\u2009cells accumulated in\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      -infected muscle, and were composed predominantly of CD206\u2009\u207a\u2009macrophages. These macrophages were positioned in direct contact with \u03b1-SMA\n                      <jats:sup>+<\/jats:sup>\n                      myofibroblasts. Moreover, numerous cells positive for both CD206 (M2 macrophage canonical marker) and \u03b1\u2011smooth muscle actin (\u03b1-SMA, biomarker of myofibroblasts) were observed. Western blot analysis revealed that S100A4 expression was restricted chiefly to M2 macrophage and its expression was markedly amplified by IL-4 together with excretory\u2013secretory (ES) products from muscle larvae of\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      . qPCR showed that inhibiting\n                      <jats:italic>S100a4<\/jats:italic>\n                      transcription reduced\n                      <jats:italic>Arg1<\/jats:italic>\n                      mRNA levels in macrophages activated by ES and IL-4. Immunofluorescence and western blot analysis showed the activated macrophages induced modest upregulation of \u03b1-SMA in fibroblasts. Immunohistochemistry revealed that inhibition of S100A4 by niclosamide reduced the expressions of CD206, TGF-\u03b21 and collagen I in\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      -infected muscle. Compared with albendazole alone, the combination of niclosamide and albendazole further reduced the larval burden in\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      -infected mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/Significance<\/jats:title>\n                    <jats:p>\n                      In conclusion, infection with\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      significantly upregulated S100A4 expression in skeletal muscle-infiltrating macrophages. S100A4 further promoted macrophage M2 polarization. The M2-like macrophages either drove fibroblast activation or acquired myofibroblast-like features, thereby fostering collagen capsule formation. Blocking S100A4 diminished macrophage M2 polarization, prevented collagen capsule formation, and represented a potential adjunctive strategy against trichinellosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014647","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:53:02Z","timestamp":1789494782000},"page":"e0014647","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["S100A4 enhances the pro-fibrotic effect of macrophage to promote collagen capsule formation of Trichinella spiralis"],"prefix":"10.1371","volume":"20","author":[{"given":"Meng Ying","family":"Gao","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Zhengzhou University","place":["Zhengzhou, People\u2019s Republic of China"],"department":["Department of Pathogen 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