{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:05:46Z","timestamp":1777417546521,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["ERAPERMED2022-245"],"award-info":[{"award-number":["ERAPERMED2022-245"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["PID2023-152752OB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2023-152752OB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n, Spain","award":["ERAPERMED2022-245"],"award-info":[{"award-number":["ERAPERMED2022-245"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n, Spain","award":["PID2023-152752OB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2023-152752OB-I00\/AEI\/10.13039\/501100011033"]}]},{"name":"Instituto de Salud Carlos III, Infrastructure of Precision Medicine associated with Science and Technology (IMPaCT) of the Strategic Action in Health (iDATA-MP)","award":["ERAPERMED2022-245"],"award-info":[{"award-number":["ERAPERMED2022-245"]}]},{"name":"Instituto de Salud Carlos III, Infrastructure of Precision Medicine associated with Science and Technology (IMPaCT) of the Strategic Action in Health (iDATA-MP)","award":["PID2023-152752OB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2023-152752OB-I00\/AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In response to vaccination and\/or infectious agents, the liver produces acute-phase proteins (APPs) driven by IL-6, which circulate in blood plasma as components of the humoral innate defense. This study investigates the liver of mice for possible effects of protective vaccination against primary blood-stage infections of Plasmodium chabaudi malaria on the expression of genes encoding APPs and IL-6 family members. Female Balb\/c mice were vaccinated with a non-infectious vaccine prior to challenge with 106\u00a0P. chabaudi-infected erythrocytes, resulting in about 80% survival of otherwise lethal infections. Gene expression microarrays were used to determine the relative transcript levels of genes in the livers of vaccinated and unvaccinated mice on days 0, 1, 4, 8, and 11 p.i. (post infectionem). Vaccination induced significant (p-value &lt; 0.05) differences in the expression of malaria-responsive genes toward the end of crisis on day 11 p.i., when mice recovered from infections. These genes include Saa4, Apcs, Cp, and Crp, encoding APPs described to inhibitorily interact with parasitic blood stages; the genes F2, F7, F8, F9, F10, and F13b, and Plg, Plat, and Serpina5, encoding proteins balancing coagulation vs. fibrinolysis dysregulated by malaria, respectively; the genes Hc, C8a, C8b, C8g, and C9, encoding components of lytic complement membrane attack complex (MAC); and Cfh, Cfi, and C4bp, encoding complement-regulatory proteins. Vaccination accelerated, albeit differently, the malaria-induced activation of all three complement pathways, evidenced as higher transcript levels of C1qa, C1qb, C1qc, Fcna, Cfp, C3, Cfh, C8a, and C9 on day 4 p.i., C1ra, C1s, and C2 on day 1 p.i., and Serping1, encoding the multifunctional protease inhibitor C1INH, on day 0 p.i. Protective vaccination may also accelerate downregulation of the malaria-promoting lethality of IL-6 trans-signaling, which may contribute to an overall accelerated recovery of mice from otherwise lethal blood-stage malaria.<\/jats:p>","DOI":"10.3390\/ijms26073173","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective Vaccination of Mice Against Blood-Stage Malaria Impacts Hepatic Expression of Genes Encoding Acute-Phase Proteins and IL-6 Family Members"],"prefix":"10.3390","volume":"26","author":[{"given":"Frank","family":"Wunderlich","sequence":"first","affiliation":[{"name":"Department of Biology, Heinrich-Heine-University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Gerovska","sequence":"additional","affiliation":[{"name":"Computational Biology and Systems Biomedicine, Biogipuzkoa Health Research Institute, 20014 San Sebastian, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Delic","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma & Co., KG, 88400 Biberach, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3264-464X","authenticated-orcid":false,"given":"Marcos J.","family":"Ara\u00fazo-Bravo","sequence":"additional","affiliation":[{"name":"Computational Biology and Systems Biomedicine, Biogipuzkoa Health Research Institute, 20014 San Sebastian, Spain"},{"name":"IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain"},{"name":"Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). 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