{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:31:19Z","timestamp":1776411079543,"version":"3.51.2"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Riley Children\u2019s Foundation"},{"name":"Indiana University Health-Indiana University School of Medicine Strategic Research Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Malaria is caused by protozoan parasites in the genus Plasmodium. Over time individuals slowly develop clinical immunity to malaria, but this process occurs at variable rates, and the mechanism of protection is not fully understood. We have recently demonstrated that in genetically identical C57BL\/6N mice, gut microbiota composition dramatically impacts the quality of the humoral immune response to Plasmodium yoelii and subsequent protection against a lethal secondary challenge with Plasmodium berghei ANKA in C57BL\/6N mice. Here, we utilize this genetically identical, gut microbiome\u2013dependent model to investigate how the gut microbiota modulate immunological memory, hypothesizing that the gut microbiome impacts the formation and functionality of immune memory. In support of this hypothesis, P. yoelii hyperparasitemia\u2013resistant C57BL\/6N mice exhibit increased protection against P. berghei ANKA\u2013induced experimental cerebral malaria (ECM) compared to P. yoelii hyperparasitemia\u2013susceptible C57BL\/6N mice. Despite differences in protection against ECM, P. yoelii\u2013resistant and \u2013susceptible mice accumulate similar numbers of memory B cells (MBCs) and memory T cells. Following challenge with P. berghei ANKA, P. yoelii\u2013resistant mice generated more rapid germinal center reactions; however, P. yoelii\u2013resistant and \u2013susceptible mice had similar titers of P. yoelii\u2013 and P. berghei\u2013specific antibodies. In contrast, P. yoelii\u2013resistant mice had an increased number of regulatory T cells in response to secondary challenge with P. berghei ANKA, which may dampen the immune-mediated breakdown of the blood\u2013brain barrier and susceptibility to P. berghei\u2013induced ECM. These findings demonstrate the ability of the gut microbiome to shape immune memory and the potential to enhance resistance to severe malaria outcomes.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf009","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T02:39:05Z","timestamp":1744079945000},"source":"Crossref","is-referenced-by-count":4,"title":["Microbiome-mediated modulation of immune memory to <i>P. yoelii<\/i> affects the resistance to secondary cerebral malaria challenge"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-4657","authenticated-orcid":false,"given":"Elizabeth M","family":"Fusco","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3650-2792","authenticated-orcid":false,"given":"Layne","family":"Bower","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]},{"name":"Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-0072","authenticated-orcid":false,"given":"Rafael","family":"Polidoro","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]},{"name":"Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen M","family":"Minns","sequence":"additional","affiliation":[{"name":"The Huck Institutes of Life Sciences, Pennsylvania State University , University Park, PA,","place":["United States"]},{"name":"Department of Biochemistry and Molecular Biology, Pennsylvania State University , University Park, PA,","place":["United States"]},{"name":"The Huck Center for Malaria Research , University Park, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1799-3726","authenticated-orcid":false,"given":"Scott E","family":"Lindner","sequence":"additional","affiliation":[{"name":"The Huck Institutes of Life Sciences, Pennsylvania State University , University Park, PA,","place":["United States"]},{"name":"Department of Biochemistry and Molecular Biology, Pennsylvania State University , University Park, PA,","place":["United States"]},{"name":"The Huck Center for Malaria Research , University Park, PA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7325-4536","authenticated-orcid":false,"given":"Nathan W","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]},{"name":"Herman B. 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