{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:09:21Z","timestamp":1774976961816,"version":"3.50.1"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007268","name":"Washington University in St. Louis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007930","name":"Institute of Clinical and Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002345"],"award-info":[{"award-number":["UL1TR002345"]}],"id":[{"id":"10.13039\/100007930","id-type":"DOI","asserted-by":"publisher"}]}],"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>Helminth infections are widespread in resource-limited settings, and modulate host immune responses, with potential implications for viral coinfections. Intestinal helminths can alter susceptibility to respiratory viruses, but the mechanisms influencing SARS-CoV-2 infection outcomes remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the Syrian hamster model, we investigated the impact of prior infection with the human hookworm\n                      <jats:italic>Ancylostoma ceylanicum<\/jats:italic>\n                      on host responses to SARS-CoV-2. Tissue-specific transcriptional responses were compared among four groups: naive, hookworm-only, SARS-CoV-2-only, and coinfected with both pathogens, 3 and 6 days post-viral infection. Viral titers and weight loss were assessed, and RNA-seq transcriptome profiles from lung and intestinal tissues were interrogated to identify differentially expressed genes and cellular pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Prior hookworm infection did not significantly alter viral titers or weight loss compared to SARS-CoV-2 infection alone, but distinct transcriptional signatures compared were identified compared to either single infection. Coinfection uniquely differentially regulated hematopoiesis and B cell-associated genes (e.g.,\n                      <jats:italic>ATF5<\/jats:italic>\n                      ,\n                      <jats:italic>IGHM<\/jats:italic>\n                      ,\n                      <jats:italic>JCHAIN<\/jats:italic>\n                      ) in the lungs, and immune and stress response pathways and inflammation-associated genes (e.g.\n                      <jats:italic>FOLR2<\/jats:italic>\n                      ,\n                      <jats:italic>PLA2GF<\/jats:italic>\n                      ,\n                      <jats:italic>FABP3<\/jats:italic>\n                      ) in the intestine. Genes and pathways differentially regulated by SARS-CoV-2 alone, but with attenuated transcriptional responses in the lungs of coinfected hamsters were observed, including the loss of upregulation of toll-like receptor signaling and previously proposed host biomarkers for COVID-19 severity (\n                      <jats:italic>CHI3L1<\/jats:italic>\n                      ,\n                      <jats:italic>HMOX1<\/jats:italic>\n                      ), Long COVID (\n                      <jats:italic>FCG4<\/jats:italic>\n                      \/\n                      <jats:italic>FCGR3A<\/jats:italic>\n                      and\n                      <jats:italic>FST<\/jats:italic>\n                      ) and mortality (\n                      <jats:italic>FST<\/jats:italic>\n                      ). In the intestine, hookworm-associated suppression of type I interferon-related genes (\n                      <jats:italic>TAP1<\/jats:italic>\n                      ,\n                      <jats:italic>IRF7<\/jats:italic>\n                      ) was reversed with SARS-CoV-2 coinfection, highlighting pathogen-specific modulation of innate antiviral signaling. Genes and pathways consistently differentially regulated by with SARS-CoV-2 were consistent with expectations, and many hemoglobin pathways were differentially regulated with hookworm in the intestine. CIBERSORT analysis was estimated relative leukocyte abundances in each sample cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that\n                      <jats:italic>A. ceylanicum<\/jats:italic>\n                      infection reshapes host transcriptional responses to SARS-CoV-2 in a tissue-specific manner, enhancing B cell immunity in the lung while driving intestinal inflammation. Hookworm-induced immune modulation attenuated key SARS-CoV-2-responsive genes and pathways, suggesting potential mechanisms for reduced disease severity observed in helminth-endemic regions. These findings establish a molecular framework to better understand helminth, SARS-CoV-2 and host immune interactions, with relevance for other respiratory viral infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1701728","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:27:32Z","timestamp":1762324052000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hookworm infection modulates lung and intestinal transcriptomic responses to SARS-CoV-2 in Syrian hamsters"],"prefix":"10.3389","volume":"16","author":[{"given":"Bruce A.","family":"Rosa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahdiyeh","family":"Bigham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamarand L.","family":"Darling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashutosh","family":"Arun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumar Sachin","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrianus C. 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