{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:38Z","timestamp":1776059018495,"version":"3.50.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"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>\n                      Trichinellosis is a globally significant zoonotic parasitic disease for which effective preventive strategies remain elusive. Our previous studies identified\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70 as a promising vaccine candidate antigen against\n                      <jats:italic>Trichinella spiralis<\/jats:italic>\n                      , although its precise mechanism of immune protection is not fully understood. Macrophages (M\u03c6) play pivotal roles in anti-helminth immunity and undergo dynamic M1\/M2 polarization shifts during different stages of\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate whether\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70 enhances host resistance against\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      infection by reprogramming macrophage polarization to provide multi-stage protection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The role of macrophages in worm expulsion was confirmed via macrophage depletion using clodronate liposomes (CloA).\n                      <jats:italic>In vivo<\/jats:italic>\n                      , cytokine levels (ELISA) and macrophage polarization (flow cytometry, immunofluorescence) were assessed in the spleen, mesenteric lymph nodes (MLN), intestine, and muscle of\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70-immunized mice at 1, 5, 15, and 30 days post-infection (dpi).\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies evaluated the direct effects of\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70 on macrophage phenotype, phagocytic capacity, and T-cell activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Macrophage depletion significantly abrogated\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70-mediated expulsion of both adult worms (early stage) and muscle larvae (mid-late stage).\n                      <jats:italic>In vivo<\/jats:italic>\n                      ,\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70 immunization promoted a sustained M1-dominated response, increased pro-inflammatory cytokines (IFN-\u03b3, TNF-\u03b1) and reduced anti-inflammatory cytokines (IL-4, IL-10) in serum. This shift significantly increased M1\/M2 ratios across peripheral organs (spleen, MLN) and local infection sites (intestine, muscle) during mid-late infection.\n                      <jats:italic>In vitro<\/jats:italic>\n                      ,\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70 directly induced M1 markers (iNOS, CD80, TNF-\u03b1), enhanced phagocytic activity, and promoted CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell proliferation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70 confers dual-stage protection against\n                      <jats:italic>T. spiralis<\/jats:italic>\n                      by sustaining M1 macrophage polarization\u2014promoting early adult worm expulsion and disrupting larval survival in later stages. These findings elucidate the mechanism underlying\n                      <jats:italic>Ts<\/jats:italic>\n                      -Hsp70-induced immune protection and reinforce its potential as an effective vaccine antigen against trichinellosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1799793","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:48:48Z","timestamp":1776055728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ts-Hsp70 confers dual-stage protective immunity against Trichinella spiralis infection by sustaining M1 macrophage polarization in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Qing","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University","place":["Beijing, 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