{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:42:57Z","timestamp":1788633777975,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fever is a common clinical symptom in patients with tuberculosis (TB). During fever, heat\u2010shock proteins (HSPs), such as HSP70, are expressed, which are molecular chaperones regulating protein folding and may also have immunomodulatory properties. How fever modulates immune responses during TB and by which mechanisms is unknown. In this study, we investigated the effects of fever, and specifically the role of HSP70, on\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb)<\/jats:italic>\n                    \u2010induced macrophage inflammatory responses. Human monocyte\u2010derived macrophages (MDM) were infected with\n                    <jats:italic>Mtb<\/jats:italic>\n                    at 37\u00b0C or 40\u00b0C to mimic febrile conditions. Fever suppresses\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2010induced IL\u20101\u03b2 and IL\u201010 gene expression and secretion from MDM, but enhances\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2010induced HSP70 secretion and intracellular accumulation in MDM. Extracellular HSP70 and HSP70\u2010expressing macrophages are abundant in granulomas in TB patient biopsies. HSP70 antagonism decreases\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2010induced IL\u20101\u03b2 secretion during febrile conditions but has no significant effect on IL\u201010 secretion. Pretreatment of MDM with recombinant HSP70 significantly increases\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2010induced IL\u20101\u03b2 at 37\u00b0C. Finally, extracellular HSP70 negatively regulates further HSP70 secretion from MDM during\n                    <jats:italic>Mtb<\/jats:italic>\n                    infection. Overall, fever and subsequent HSP70 expression modulates proinflammatory innate immune response in TB, which may have implications for the development of host\u2010directed therapies.\n                  <\/jats:p>","DOI":"10.1002\/eji.202551963","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T04:13:07Z","timestamp":1752725587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fever\u2010Induced Heat Shock Protein\u201070 Regulates Macrophage IL\u20101\u03b2 and IL\u201010 Secretion During\n                    <i>Mycobacterium tuberculosis<\/i>\n                    Infection"],"prefix":"10.1002","volume":"55","author":[{"given":"Deborah L. W.","family":"Chong","sequence":"first","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajeel A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kutschenreuter","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramla","family":"Cusman","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena Murugananden","family":"Pillai","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-8541","authenticated-orcid":false,"given":"Daniela E.","family":"Kirwan","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Gilman","sequence":"additional","affiliation":[{"name":"Department of International Health Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon S.","family":"Friedland","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Global Tuberculosis Report 2024","author":"World Health Organization","year":"2024"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp2118145"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042120-032916"},{"key":"e_1_2_11_5_1","volume-title":"Global Tuberculosis Report 2022","author":"World Health Organization","year":"2022"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.88"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45666"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3843"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.17.1870"},{"issue":"12","key":"e_1_2_11_10_1","first-page":"1178","article-title":"Extra\u2010Pulmonary Manifestations in a Large Metropolitan Area With a Low Incidence of Tuberculosis","volume":"7","author":"Gonzalez O. 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