{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:56:58Z","timestamp":1791881818941,"version":"4.3.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cryptococcus causes life-threatening infections; however, immune programs driving the pathogenesis of these infections in the human host remain incompletely described. We leveraged whole-blood transcriptomic analysis to define distinct, conserved elements of the host immune response in participants with cryptococcal infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RNA sequencing was performed on whole blood from adult febrile inpatients admitted to 2 hospitals in Moshi, Tanzania, to compare gene expression between participants with cryptococcal, bacterial, or viral diseases, and adult community controls. Differential expression and gene set enrichment analyses were used to characterize expression differences between pathogen-class groups. Penalized logistic regression was used to identify gene expression signatures capable of identifying Cryptococcus disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Out of 118 participants, 13 (11%) had cryptococcal disease, and 41 (34.7%) were persons with HIV (PWH). Genes upregulated in response to cryptococcosis compared to nonacutely infected community controls reflected complement activation, neutrophil activation, type I interferon signaling, and myeloid dendritic cell differentiation. When compared to combined bacterial or viral illnesses, cryptococcal disease demonstrated hyperactivation of both innate and humoral immune pathways. A series of classifiers were developed that distinguished between cryptococcal and combined bacterial or viral diseases with an AUC of 0.946.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, the host response to cryptococcosis in individuals with advanced HIV, as manifested in transcriptional profiles, informs our understanding of the pathophysiology of and susceptibility to cryptococcal infection and may support the development of novel diagnostic and therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag497","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:57:57Z","timestamp":1790769477000},"source":"Crossref","is-referenced-by-count":0,"title":["The Host Transcriptional Response to Real-world Cryptococcosis in the Setting of Advanced HIV Disease Defines Dysregulated Immune Responses That Underlie Increased Vulnerability to Infection"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-4476","authenticated-orcid":false,"given":"Beatrice Z","family":"Sim","sequence":"first","affiliation":[{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]},{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-3647","authenticated-orcid":false,"given":"Julie M","family":"Steinbrink","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4387-6398","authenticated-orcid":false,"given":"Alejandro","family":"Antonia","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Andrew","family":"Alspaugh","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4023-3928","authenticated-orcid":false,"given":"Deng B","family":"Madut","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]},{"name":"Duke Global Health Institute, Duke University , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3187-5905","authenticated-orcid":false,"given":"Manuela","family":"Carugati","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4529-102X","authenticated-orcid":false,"given":"John A","family":"Crump","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department of Medicine, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]},{"name":"Duke Global Health Institute, Duke University , Durham, North Carolina ,","place":["USA"]},{"name":"School of Medicine, Kilimanjaro Christian Medical Centre University , Moshi ,","place":["Tanzania"]},{"name":"Centre for International Health, University of Otago , Dunedin ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-1916","authenticated-orcid":false,"given":"Blandina T","family":"Mmbaga","sequence":"additional","affiliation":[{"name":"Duke Global Health Institute, Duke University , Durham, North Carolina ,","place":["USA"]},{"name":"School of Medicine, Kilimanjaro Christian Medical Centre University , Moshi ,","place":["Tanzania"]},{"name":"Kilimanjaro Christian Medical Centre , Moshi ,","place":["Tanzania"]},{"name":"Department of Research, Kilimanjaro Clinical Research Institute , Moshi ,","place":["Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S","family":"Ngocho","sequence":"additional","affiliation":[{"name":"Kilimanjaro Christian Medical Centre , Moshi ,","place":["Tanzania"]},{"name":"Department of Research, Kilimanjaro Clinical Research Institute , Moshi ,","place":["Tanzania"]},{"name":"School of Public Health, Kilimanjaro Christian Medical Centre University , Moshi ,","place":["Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asia H","family":"Kipengele","sequence":"additional","affiliation":[{"name":"Kilimanjaro Christian Medical Centre , Moshi ,","place":["Tanzania"]},{"name":"Department of Research, Kilimanjaro Clinical Research Institute , Moshi ,","place":["Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philoteus A","family":"Sakasaka","sequence":"additional","affiliation":[{"name":"School of Medicine, Kilimanjaro Christian Medical Centre University , Moshi ,","place":["Tanzania"]},{"name":"Kilimanjaro Christian Medical Centre , Moshi ,","place":["Tanzania"]},{"name":"Department of Research, Kilimanjaro Clinical Research Institute , Moshi ,","place":["Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel H","family":"Kalengo","sequence":"additional","affiliation":[{"name":"School of Medicine, Kilimanjaro Christian Medical Centre University , Moshi ,","place":["Tanzania"]},{"name":"Kilimanjaro Christian Medical Centre , Moshi ,","place":["Tanzania"]},{"name":"Department of Research, Kilimanjaro Clinical Research Institute , Moshi ,","place":["Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3838-0312","authenticated-orcid":false,"given":"Venance P","family":"Maro","sequence":"additional","affiliation":[{"name":"School of Medicine, Kilimanjaro Christian Medical Centre University , Moshi ,","place":["Tanzania"]},{"name":"Kilimanjaro Christian Medical Centre , Moshi ,","place":["Tanzania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5262-1421","authenticated-orcid":false,"given":"Matthew P","family":"Rubach","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Department 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