{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:21:26Z","timestamp":1785424886175,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,10]]},"group-title":"Immunology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["K08AI130366"],"award-info":[{"award-number":["K08AI130366"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI162765"],"award-info":[{"award-number":["R01AI162765"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32HL170963"],"award-info":[{"award-number":["T32HL170963"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                  is an opportunistic fungus that causes pulmonary and central nervous system infections after entry into the lungs. We previously established that signaling through the adapter protein DAP12 inhibits the antifungal response of monocyte-derived macrophages and worsens the survival of mice after\n                  <jats:italic>C. neoformans<\/jats:italic>\n                  infection. However, the molecular mechanisms by which DAP12 signaling is initiated during cryptococcosis remain inadequately characterized. In this study, we identify triggering receptor expressed on myeloid cells 2 (TREM2) as a DAP12-associated receptor that is induced on murine monocytes and interstitial macrophages in the lungs in response to\n                  <jats:italic>C. neoformans<\/jats:italic>\n                  infection. TREM2 subsequently represses fungal uptake and M1 polarization by monocyte-derived macrophages. Using an\n                  <jats:italic>in vitro<\/jats:italic>\n                  binding assay, we find that both murine and human TREM2 can directly bind to\n                  <jats:italic>C. neoformans<\/jats:italic>\n                  and that the absence of the cryptococcal cell wall antigen \u03b2-1,6-glucan disrupts these interactions. Overall, our findings suggest that the TREM2-DAP12 pathway plays an important inhibitory role in the host immune response to cryptococcal infection by impeding macrophage activation and phagocytosis of fungal cells. We also establish TREM2 as a receptor involved in direct fungal sensing of\n                  <jats:italic>C. neoformans<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.64898\/2026.06.10.731331","type":"posted-content","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:45:24Z","timestamp":1781153124000},"source":"Crossref","is-referenced-by-count":0,"title":["TREM2 drives monocyte-derived macrophage responses to\n                  <i>Cryptococcus neoformans<\/i>"],"prefix":"10.64898","author":[{"given":"Adiza","family":"Abass","sequence":"first","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Ricafrente","sequence":"additional","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurwa","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Vichaidit","sequence":"additional","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aelita","family":"Arshakyan","sequence":"additional","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreemoyee","family":"Acharya","sequence":"additional","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-575X","authenticated-orcid":false,"given":"Lena J.","family":"Heung","sequence":"additional","affiliation":[{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Medicine, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"},{"name":"Department of Biomedical Sciences, Cedars-Sinai Health Sciences University, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061514550545000_2026.06.10.731331v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2006.07.001"},{"key":"2026061514550545000_2026.06.10.731331v2.2","doi-asserted-by":"crossref","unstructured":"Heung LJ . 2017. 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