{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:51:25Z","timestamp":1785599485609,"version":"3.56.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      \u03b3\u03b4 T cells play a key role in modulating immune responses to pregnancy-associated malaria and can enhance vaccine efficacy through their activation and cytotoxic functions. However, the mechanisms guiding \u03b3\u03b4T cell differentiation in placental malaria (PM) remain poorly understood. We examined\n                      <jats:italic>ex vivo<\/jats:italic>\n                      associations between cytokines, metabolic profiles and \u03b3\u03b4 T-cell differentiation in women with PM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A case-control study including 50 women at delivery (21 PM+, 29 PM-) was carried out. Peripheral, placental intervillous space, and cord blood mononuclear cells were isolated, and multiparametric flow cytometry was performed to characterize \u03b3\u03b4T-cells and memory phenotypes, its subsets (V\u03b41\n                      <jats:sup>+<\/jats:sup>\n                      , V\u03b42\n                      <jats:sup>+<\/jats:sup>\n                      , V\u03b43\n                      <jats:sup>+<\/jats:sup>\n                      ), and the expression of exhaustion (TIM-3, PD1) and activation (HLA-DR) markers.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      plasma levels of IL-8, IL-33, and IL-35 were quantified by Luminex assay or ELISA. Immunometabolic profiles were assessed in a subset of 15 samples from uninfected women following cell stimulation with phytohemagglutinin (PHA) by SCENITH assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In general, the frequency of \u03b3\u03b4 T cells and their subsets varied depending on the different blood compartments, with na\u00efve and central memory (CM) phenotypes observed mainly in CBMC, while effector memory (EM) and terminally differentiated effector memory (TEMRA) phenotypes were found mainly in PBMC and IVBMC.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      analyses showed that \u03b3\u03b4 T cell-modulating cytokine IL-8 were associated, in a compartment-dependent manner, with down-regulation of immunoregulatory markers TIM-3 and PD-1. Interestingly, IL-8 and IL-33 were associated with increased frequency of the TEMRA cell phenotype in peripheral blood, consistent with enhanced differentiation of na\u00efve \u03b3\u03b4T cells during PM. Metabolic profiling of the different cell types further established an enhanced mitochondrial metabolic activity in predominantly terminally differentiated \u03b3\u03b4 T cells in PBMC, compared to the mainly glycolytic activities of non-terminally differentiated cells in CBMC and IVBMC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Placental malaria is associated with a compartment-specific memory \u03b3\u03b4 T cell differentiation, with cytokines and metabolic reprogramming regulating exhaustion. These findings reveal key regulatory processes that determine the function of \u03b3\u03b4 T cells during placental malaria, which constitute potential targets for new therapeutic intervention against PM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803384","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:21:13Z","timestamp":1776313273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Ex vivo cytokine responses and metabolic reprogramming are associated with \u03b3\u03b4 T cell differentiation in Plasmodium falciparum placental malaria"],"prefix":"10.3389","volume":"17","author":[{"given":"Chris Marco","family":"Nana Mbianda","sequence":"first","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]},{"name":"Immunology Laboratory of the Biotechnology Center, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodin Darcisse","family":"Kwanou Tchakounte","sequence":"additional","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]},{"name":"Immunology Laboratory of the Biotechnology Center, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard Marie","family":"Bitye Zambo","sequence":"additional","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]},{"name":"Immunology Laboratory of the Biotechnology Center, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9phine","family":"Ntankheuh Tchinkou","sequence":"additional","affiliation":[{"name":"Immunology Laboratory of the Biotechnology Center, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]},{"name":"Department of Microbiology, Faculty of Sciences, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick","family":"Atchombat Nyasse","sequence":"additional","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]},{"name":"Immunology Laboratory of the Biotechnology Center, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balotin","family":"Fogang","sequence":"additional","affiliation":[{"name":"Malaria Research Unit, Centre Pasteur du Cameroun","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Jos\u00e9","family":"Arg\u00fcello","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, CNRS, INSERM, CIML, Centre d\u2019Immunologie de Marseille","place":["Marseille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Ayong","sequence":"additional","affiliation":[{"name":"Malaria Research Unit, Centre Pasteur du Cameroun","place":["Yaound\u00e9, Cameroon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosette","family":"Megnekou","sequence":"additional","affiliation":[{"name":"Department of Animal Biology and Physiology, Faculty of Sciences, University of Yaound\u00e9 I","place":["Yaound\u00e9, Cameroon"]},{"name":"Immunology Laboratory of the Biotechnology Center, University of Yaound\u00e9 I","place":["Yaound\u00e9, 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