{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T02:41:13Z","timestamp":1768617673402,"version":"3.49.0"},"posted":{"date-parts":[[2024,1,21]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull\u2019s rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase\/signal transducer and activator of transcription (JAK\/STAT) activation. JAK\/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44\n                  <jats:sup>hi<\/jats:sup>\n                  CD62\n                  <jats:sup>lo<\/jats:sup>\n                  CD4\n                  <jats:sup>+<\/jats:sup>\n                  effector CD4\n                  <jats:sup>+<\/jats:sup>\n                  T-cells and MHC II\n                  <jats:sup>+<\/jats:sup>\n                  inflammatory myeloid cells, and weight gains in mice, the latter after treatment with antifungals. Based on these data, pathway-driven steroid-sparing human treatment for steroid-refractory PIIRS was initiated using short courses of the JAK\/STAT inhibitor ruxolitinib. These were well tolerated and reduced activated HLA-DR\n                  <jats:sup>+<\/jats:sup>\n                  CD4\n                  <jats:sup>+<\/jats:sup>\n                  and CD8\n                  <jats:sup>+<\/jats:sup>\n                  cells and inflammatory monocytes as well as improved brain imaging. Together, these findings support the role of JAK\/STAT in PIIRS as well as further study of JAK\/STAT inhibitors as potential adjunctive therapy for PIRS and other neural inflammatory syndromes.\n                <\/jats:p>","DOI":"10.1101\/2024.01.18.24301483","type":"posted-content","created":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T21:45:12Z","timestamp":1705873512000},"source":"Crossref","is-referenced-by-count":2,"title":["JAK\/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8724-9463","authenticated-orcid":false,"given":"Jessica C.","family":"Hargarten","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8125-0698","authenticated-orcid":false,"given":"Kenneth","family":"Ssebambulidde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seher H.","family":"Anjum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0645-6510","authenticated-orcid":false,"given":"Malcolm J.","family":"Vaughan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-8601","authenticated-orcid":false,"given":"Jintao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7228-7827","authenticated-orcid":false,"given":"Anutosh","family":"Ganguly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon-dong","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-7871","authenticated-orcid":false,"given":"Dima A.","family":"Hammoud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-0843","authenticated-orcid":false,"given":"Michal A.","family":"Olszewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-2178","authenticated-orcid":false,"given":"Peter R.","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024012312101050000_2024.01.18.24301483v1.1","doi-asserted-by":"crossref","unstructured":"Pirofski LA , Casadevall A . 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