{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:46:17Z","timestamp":1787060777178,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["210879364"],"award-info":[{"award-number":["210879364"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["031L0291B"],"award-info":[{"award-number":["031L0291B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003107","name":"Federal Ministry of Health, Germany","doi-asserted-by":"publisher","award":["1369\u2013240"],"award-info":[{"award-number":["1369\u2013240"]}],"id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Candida albicans is a leading cause of invasive candidiasis, a life-threatening infection with high mortality despite antifungal therapy. Echinocandins are first-line agents due to their fungicidal activity and low toxicity profile. Beyond direct killing, they may also modulate host immunity, e.g. through fungal cell wall remodeling. However, the systemic impact of echinocandins on human immune cells remains incompletely understood, particularly in the context of drug resistance. Using an ex vivo human whole-blood infection model, we assessed the effects of caspofungin during infection with echinocandin-susceptible (ECHS\/FKSwt) and echinocandin-resistant (ECHR\/FKSmut) C. albicans strains. Infection alone triggered a strong and conserved transcriptional immune program enriched for innate recognition and inflammatory pathways. Caspofungin treatment during infection with the susceptible strain selectively amplified these responses, engaging a sequential cascade of host defenses that linked pathogen recognition with innate effector functions and adaptive polarisation. In contrast, caspofungin induced only minimal transcriptional changes in resistant strain infections or in uninfected blood. These findings demonstrate that caspofungin efficacy arises not only from its fungicidal activity but also from amplification of host immunity, an effect primarily dependent on fungal susceptibility. This dual mode of action highlights a previously underappreciated role of echinocandins in shaping antifungal immunity and provides new mechanistic insight into drug-host\u2013pathogen interactions during systemic candidiasis.<\/jats:p>","DOI":"10.1093\/femsml\/uqag004","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:46:02Z","timestamp":1769690762000},"source":"Crossref","is-referenced-by-count":2,"title":["Caspofungin enhances antifungal immunity in human blood through transcriptional reprogramming"],"prefix":"10.1093","volume":"7","author":[{"given":"Aia","family":"Shehata","sequence":"first","affiliation":[{"name":"Institute for Hygiene and Microbiology, Julius Maximilians University of W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]},{"name":"Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute Research Group Fungal Septomics, , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-6546","authenticated-orcid":false,"given":"Sascha","family":"Sch\u00e4uble","sequence":"additional","affiliation":[{"name":"Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, Julius Maximilians University of W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Maximilian","family":"Aldejohann","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, Julius Maximilians University of W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]},{"name":"National Reference Center for Invasive Fungal Infections (NRZMyk), Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0128-3076","authenticated-orcid":false,"given":"Gianni","family":"Panagiotou","sequence":"additional","affiliation":[{"name":"Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute , 07745 Jena ,","place":["Germany"]},{"name":"Faculty of Biological Sciences, Friedrich Schiller University , 07743 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Kurzai","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, Julius Maximilians University of W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]},{"name":"Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute Research Group Fungal Septomics, , 07745 Jena ,","place":["Germany"]},{"name":"National Reference Center for Invasive Fungal Infections (NRZMyk), Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-0484","authenticated-orcid":false,"given":"Kerstin","family":"H\u00fcnniger-Ast","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, Julius Maximilians University of W\u00fcrzburg , 97080 W\u00fcrzburg ,","place":["Germany"]},{"name":"Leibniz Institute for Natural Product Research and Infection Biology - Hans Kn\u00f6ll Institute Research Group Fungal Septomics, , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"2026021416513810600_bib1","doi-asserted-by":"publisher","first-page":"dlab122","DOI":"10.1093\/jacamr\/dlab122","article-title":"Emergence of resistant Candida glabrata in Germany","volume":"3","author":"Aldejohann","year":"2021","journal-title":"JAC Antimicrob Resist"},{"key":"2026021416513810600_bib2","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"2026021416513810600_bib3","doi-asserted-by":"publisher","first-page":"e01628","DOI":"10.1128\/AAC.01628-18","article-title":"Comparative genomics of serial Candida glabrata isolates and the rapid acquisition of echinocandin resistance during therapy","volume":"63(2)","author":"Barber","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2026021416513810600_bib5","doi-asserted-by":"publisher","first-page":"bau126","DOI":"10.1093\/database\/bau126","article-title":"Comparison of human cell signaling pathway databases\u2013evolution, drawbacks and challenges","volume":"2015","author":"Chowdhury","year":"2015","journal-title":"Database (Oxford)"},{"key":"2026021416513810600_bib6","doi-asserted-by":"publisher","first-page":"e280","DOI":"10.1016\/S1473-3099(24)00749-7","article-title":"Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM","volume":"25","author":"Cornely","year":"2025","journal-title":"Lancet Infect Dis"},{"key":"2026021416513810600_bib7","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3390\/microorganisms8020154","article-title":"Candida albicans antifungal resistance and tolerance in bloodstream infections: the triad yeast-host-antifungal","volume":"8(2)","author":"Costa-de-Oliveira","year":"2020","journal-title":"Microorganisms"},{"key":"2026021416513810600_bib8","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"2026021416513810600_bib9","first-page":"316","article-title":"Host response to Candida albicans bloodstream infection and sepsis","volume":"6","author":"Duggan","year":"2015","journal-title":"Virulence"},{"key":"2026021416513810600_bib10","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2147\/tcrm.2007.3.1.71","article-title":"Comparison of echinocandin antifungals","volume":"3","author":"Eschenauer","year":"2007","journal-title":"Ther Clin Risk Manag"},{"key":"2026021416513810600_bib11","doi-asserted-by":"publisher","first-page":"4581","DOI":"10.1038\/s41598-022-08738-4","article-title":"Antifungals influence the immune-related transcriptomic landscape of human monocytes after Aspergillus fumigatus infection","volume":"12","author":"Henry","year":"2022","journal-title":"Sci Rep"},{"key":"2026021416513810600_bib12","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1086\/589304","article-title":"Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal beta-glucan exposure","volume":"198","author":"Hohl","year":"2008","journal-title":"J Infect Dis"},{"key":"2026021416513810600_bib13","doi-asserted-by":"publisher","first-page":"e1003479","DOI":"10.1371\/journal.pcbi.1003479","article-title":"A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood","volume":"10","author":"H\u00fcnniger","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"2026021416513810600_bib14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.trsl.2020.07.005","article-title":"Caspofungin suppresses zymosan-induced cytokine and chemokine release in THP-1 cells: possible involvement of the spleen tyrosine kinase pathway","volume":"227","author":"Itoh","year":"2021","journal-title":"Transl Res"},{"key":"2026021416513810600_bib15","first-page":"e02435","article-title":"Survival strategies of pathogenic Candida species in Human blood show independent and specific adaptations","volume":"11(5)","author":"K\u00e4mmer","year":"2020","journal-title":"mBio"},{"key":"2026021416513810600_bib16","doi-asserted-by":"publisher","first-page":"e0002123","DOI":"10.1128\/mmbr.00021-23","article-title":"Candida albicans and Candida glabrata: global priority pathogens","volume":"88","author":"Katsipoulaki","year":"2024","journal-title":"Microbiol Mol Biol Rev"},{"key":"2026021416513810600_bib17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/myc.13386","article-title":"Human plasma protein levels alter the in vitro antifungal activity of caspofungin: an explanation to the effect in critically ill?","volume":"65","author":"Kurland","year":"2022","journal-title":"Mycoses"},{"key":"2026021416513810600_bib18","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1128\/AAC.00683-11","article-title":"Elevated cell wall chitin in Candida albicans confers echinocandin resistance in vivo","volume":"56","author":"Lee","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2026021416513810600_bib19","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/jac\/dkg117","article-title":"Caspofungin: the first representative of a new antifungal class","volume":"51","author":"Letscher-Bru","year":"2003","journal-title":"J Antimicrob Chemother"},{"key":"2026021416513810600_bib20","first-page":"189","article-title":"Candida albicans the main opportunistic pathogenic fungus in humans","volume":"55","author":"Macias-Paz","year":"2023","journal-title":"Rev Argent Microbiol"},{"key":"2026021416513810600_bib21","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/j.1439-0507.2005.01131.x","article-title":"Pharmacological properties and clinical efficacy of a recently licensed systemic antifungal, caspofungin","volume":"48","author":"Maschmeyer","year":"2005","journal-title":"Mycoses"},{"key":"2026021416513810600_bib22","doi-asserted-by":"publisher","first-page":"1620179","DOI":"10.3389\/fphar.2025.1620179","article-title":"Predictors of caspofungin exposure-response relationship: a retrospective cohort study on therapeutic drug monitoring parameters","volume":"16","author":"Meng","year":"2025","journal-title":"Front Pharmacol"},{"key":"2026021416513810600_bib23","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1128\/IAI.01282-10","article-title":"Recognition and blocking of innate immunity cells by Candida albicans chitin","volume":"79","author":"Mora-Montes","year":"2011","journal-title":"Infect Immun"},{"key":"2026021416513810600_bib24","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1093\/jac\/dkm125","article-title":"Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit","volume":"60","author":"Nguyen","year":"2007","journal-title":"J Antimicrob Chemother"},{"key":"2026021416513810600_bib25","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1186\/s12864-017-4097-4","article-title":"Dual transcriptome of the immediate neutrophil and Candida albicans interplay","volume":"18","author":"Niemiec","year":"2017","journal-title":"BMC Genomics [Electronic Resource]"},{"key":"2026021416513810600_bib26","doi-asserted-by":"publisher","first-page":"S612","DOI":"10.1093\/cid\/civ791","article-title":"Echinocandin resistance in Candida","volume":"61","author":"Perlin","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2026021416513810600_bib27","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41579-025-01174-x","article-title":"Commensalism and pathogenesis of Candida albicans at the mucosal interface","volume":"23","author":"Schille","year":"2025","journal-title":"Nat Rev Micro"},{"key":"2026021416513810600_bib28","article-title":"GEO2RNAseq: an easy-to-use R pipeline for complete pre-processing of RNA-seq data","author":"Seelbinder","year":"2019","journal-title":"bioRxiv"},{"key":"2026021416513810600_bib29","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1038\/ncomms2343","article-title":"Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans","volume":"4","author":"Smeekens","year":"2013","journal-title":"Nat Commun"},{"key":"2026021416513810600_bib30","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1128\/AAC.01486-12","article-title":"Elevated chitin content reduces the susceptibility of Candida species to caspofungin","volume":"57","author":"Walker","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2026021416513810600_bib31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.3389\/fcimb.2020.00164","article-title":"Caspofungin induced cell wall changes of Candida species influences macrophage interactions","volume":"10","author":"Walker","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"2026021416513810600_bib32","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1371\/journal.ppat.0020035","article-title":"A drug-sensitive genetic network masks fungi from the immune system","volume":"2","author":"Wheeler","year":"2006","journal-title":"PLoS Pathog"},{"key":"2026021416513810600_bib33","doi-asserted-by":"publisher","first-page":"e1000227","DOI":"10.1371\/journal.ppat.1000227","article-title":"Dynamic, morphotype-specific Candida albicans beta-glucan exposure during infection and drug treatment","volume":"4","author":"Wheeler","year":"2008","journal-title":"PLoS Pathog"},{"key":"2026021416513810600_bib34","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1128\/AAC.01912-12","article-title":"Population pharmacokinetics of escalating doses of caspofungin in a phase II study of patients with invasive aspergillosis","volume":"57","author":"W\u00fcrthwein","year":"2013","journal-title":"Antimicrob Agents Chemother"}],"container-title":["microLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/microlife\/advance-article-pdf\/doi\/10.1093\/femsml\/uqag004\/66640627\/uqag004.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/microlife\/article-pdf\/doi\/10.1093\/femsml\/uqag004\/66640627\/uqag004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/microlife\/article-pdf\/doi\/10.1093\/femsml\/uqag004\/66640627\/uqag004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:51:45Z","timestamp":1771105905000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/microlife\/article\/doi\/10.1093\/femsml\/uqag004\/8445400"}},"subtitle":[],"editor":[{"given":"Carmen","family":"Buchrieser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":33,"URL":"https:\/\/doi.org\/10.1093\/femsml\/uqag004","relation":{},"ISSN":["2633-6693"],"issn-type":[{"value":"2633-6693","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"uqag004"}}