{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:20:35Z","timestamp":1792138835942,"version":"4.4.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"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:p><jats:italic>Toxoplasma gondii<\/jats:italic>, a zoonotic apicomplexan that infects over a billion people worldwide, can cause early death in immunocompromised individuals and defects in foetal brain development. <jats:italic>Toxoplasma<\/jats:italic> is also a major cause of abortion in small ruminants. When <jats:italic>Toxoplasma<\/jats:italic> encounters host cells, several outcomes are possible. For example, the parasite can enter the host cell or can inject its effector proteins into the cell without entering. These heterogenous outcomes occur simultaneously in the same host and likely determine disease pathogenesis. Yet, current knowledge of host-<jats:italic>Toxoplasma<\/jats:italic> interactions is largely based on averaged responses in bulk cell populations. Here, we employed single cell RNA (scRNA) and bulk RNA sequencing to investigate the transcriptional profiles that underpin heterogenous host-<jats:italic>Toxoplasma<\/jats:italic> interaction in human peripheral blood mononuclear cells. We observed that <jats:italic>Toxoplasma<\/jats:italic> preferentially infects and elicits transcriptional responses in dendritic cells in human blood. Additionally, we observed that monocytes adopt a dendritic cell-like transcriptional profile over the course of infection. Using genes expressed in sorted host cell populations representative of the different heterogenous host-<jats:italic>Toxoplasma<\/jats:italic> interaction outcomes as a reference panel, we show that genes expressed in cells infected via phagocytosis are largely expressed in dendritic cells. Thus, by integrating scRNA and bulk RNA sequencing, our study unveils the transcriptional profiles of diverse <jats:italic>Toxoplasma<\/jats:italic>-host cell interaction outcomes, providing novel avenues for targeted investigations into host gene functions during <jats:italic>Toxoplasma<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1582645","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T04:10:25Z","timestamp":1750738225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual single-cell and bulk RNA sequencing reveal transcriptional profiles underlying heterogenous host-parasite interactions in human peripheral blood mononuclear cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Praveena","family":"Chandrasegaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekir","family":"Faydaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa A.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"B1","unstructured":"Toxoplasma gondii: from animals to humans\n          \n          \n            \n              Tenter\n              AM\n            \n            \n              Heckeroth\n              AR\n            \n            \n              Weiss\n              LM\n            \n          \n          Int J Parasitol\n          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Vectors"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004047","article-title":"Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to toxoplasma gondii","volume":"10","author":"Dupont","year":"2014","journal-title":"PloS Pathog"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316841111","article-title":"Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome","volume":"111","author":"Zhao","year":"2014","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501558","article-title":"The IL-12 response of primary human dendritic cells and monocytes to toxoplasma gondii is stimulated by phagocytosis of live parasites rather than host cell invasion","volume":"196","author":"Tosh","year":"2016","journal-title":"J 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Patients with defective NK cell function have problems with herpesvirus infections cell activation and cytotoxicity that can override the","volume":"14","author":"Cosman","year":"2001","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7331","article-title":"Early growth response gene-2, a zinc-finger transcription factor, is required for full induction of clonal anergy in CD4+ T cells","volume":"173","author":"Harris","year":"2004","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ni1193","article-title":"Egr-2 and Egr-3 are negative regulators of T cell activation","volume":"6","author":"Safford","year":"2005","journal-title":"Nat Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160553","article-title":"Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation","volume":"214","author":"Miao","year":"2017","journal-title":"J Exp Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2017.09.007","article-title":"CISH controls bacterial burden early after infection with Mycobacterium tuberculosis in mice","volume":"107","author":"Carow","year":"2017","journal-title":"Tuberculosis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.08.101","article-title":"Mycobacterium tuberculosis controls phagosomal acidification by targeting CISH-mediated signaling","volume":"20","author":"Queval","year":"2017","journal-title":"Cell Rep"},{"key":"B32","article-title":"In Vivo Microbial Stimulation Induces Rapid CD40 Ligand-independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas","author":"Caetano Reis Sousa","year":"1997","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4822-4826.2000","article-title":"Differential infectivity and division of toxoplasma gondii in human peripheral blood leukocytes","volume":"68","author":"Channon","year":"2000","journal-title":"Infect And Immun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.06.021","article-title":"Migration and maturation of human dendritic cells infected with Toxoplasma gondii depend on parasite strain type","volume":"42","author":"Diana","year":"2004","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.31","article-title":"Cutting Edge: Dendritic Cells Are Essential for In Vivo IL-12 Production and Development of Resistance against Toxoplasma gondii Infection in Mice","volume":"177","author":"Liu","year":"2006","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.01.017","article-title":"Monocyte-Derived Dendritic Cells Formed at the Infection Site Control the Induction of Protective T Helper 1 Responses against Leishmania","volume":"26","author":"Le\u00f3n","year":"2007","journal-title":"Immunity"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80149-1","article-title":"Differentiation of Phagocytic Monocytes into Lymph Node Dendritic Cells In Vivo differentiate into DCs in an in vitro model of transendo-thelial trafficking without addition of exogenous cyto-kines (Randolph et\u00a0al., 1998), supporting the idea that most efficiently when they receive a phagocytic stimulus during their transient residence in subendothelial matrix","volume":"42","author":"Randolph","year":"1999","journal-title":"Immunity"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242480","article-title":"Role of inflammatory dendritic cells in innate and adaptive immunity","volume":"42","author":"Hespel","year":"2012","journal-title":"Eur J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/697972","article-title":"Monocytes, peripheral blood mononuclear cells, and THP-1 cells exhibit different cytokine expression patterns following stimulation with lipopolysaccharide","volume":"2013","author":"Schildberger","year":"2013","journal-title":"Mediators Inflammation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.molimm.2017.05.027","article-title":"THP-1 and human peripheral blood mononuclear cell-derived macrophages differ in their capacity to polarize in vitro. 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