{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:57:03Z","timestamp":1787911023353,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011051","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U19AI128914"],"award-info":[{"award-number":["U19AI128914"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U19AI128914"],"award-info":[{"award-number":["U19AI128914"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["GHVAP NG-ID18-Stuart"],"award-info":[{"award-number":["GHVAP NG-ID18-Stuart"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P41GM109824"],"award-info":[{"award-number":["P41GM109824"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated <jats:italic>Plasmodium falciparum<\/jats:italic> sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malarial infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with type I and II interferon and NK cell responses were increased in prior to CHMI while T and B cell signatures were decreased as early as one day following CHMI in protected vaccinees. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of v\u03b42+ \u03b3\u03b4 T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that vaccine-induced immune response is heterogenous between protected and non-protected vaccinees and that inducted-malaria protection by PfRAS is associated with early and rapid changes in interferon, NK cell and adaptive immune responses.<\/jats:p>\n<jats:p><jats:bold>Trial Registration<\/jats:bold>: ClinicalTrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01994525\" xlink:type=\"simple\">NCT01994525<\/jats:ext-link>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011051","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T17:42:04Z","timestamp":1684345324000},"page":"e1011051","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge"],"prefix":"10.1371","volume":"19","author":[{"given":"Damian A.","family":"Oyong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergal J.","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell L.","family":"Neal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Carnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine V.","family":"Schwedhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hertoghs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Hwan","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Aitchison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"De Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan W.","family":"Newell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Juliana","family":"McElrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-9758","authenticated-orcid":true,"given":"Kenneth D.","family":"Stuart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ppat.1011051.ref001","unstructured":"WHO. World malaria report 2021. Geneva; 2021."},{"key":"ppat.1011051.ref002","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","article-title":"Efficacy and safety of RTS,S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial.","volume":"386","author":"RTS SCTP","year":"2015","journal-title":"Lancet"},{"key":"ppat.1011051.ref003","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(21)00943-0","article-title":"Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial","volume":"397","author":"MS Datoo","year":"2021","journal-title":"Lancet"},{"key":"ppat.1011051.ref004","article-title":"The Importance of Exercising Caution When Comparing Results from Malaria Vaccines Administered on the EPI Schedule and on a Seasonal Schedule","author":"A Birkett","year":"2022","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1011051.ref005","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1056\/NEJMoa0805832","article-title":"Protection against a malaria challenge by sporozoite inoculation","volume":"361","author":"M Roestenberg","year":"2009","journal-title":"N Engl J Med"},{"key":"ppat.1011051.ref006","first-page":"14","article-title":"A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection","author":"SC Murphy","year":"2022","journal-title":"Sci Transl Med"},{"key":"ppat.1011051.ref007","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nature03188","article-title":"Genetically modified Plasmodium parasites as a protective experimental malaria vaccine","volume":"433","author":"A-K Mueller","year":"2005","journal-title":"Nature"},{"key":"ppat.1011051.ref008","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1016\/j.vaccine.2008.11.073","article-title":"The Effects of radiation on the safety and protective efficacy of an attenuated Plasmodium yoelii sporozoite malaria vaccine","volume":"27","author":"R Chattopadhyay","year":"2009","journal-title":"Vaccine"},{"key":"ppat.1011051.ref009","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1126\/science.1211548","article-title":"Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity","volume":"334","author":"JE Epstein","year":"2011","journal-title":"Science"},{"key":"ppat.1011051.ref010","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1086\/339409","article-title":"Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites","volume":"185","author":"SL Hoffman","year":"2002","journal-title":"J Infect Dis"},{"key":"ppat.1011051.ref011","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1016\/S0140-6736(11)60360-7","article-title":"Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study","volume":"377","author":"M Roestenberg","year":"2011","journal-title":"Lancet"},{"key":"ppat.1011051.ref012","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4269\/ajtmh.17-1014","article-title":"Safety, Immunogenicity, and Protective Efficacy against Controlled Human Malaria Infection of Plasmodium falciparum Sporozoite Vaccine in Tanzanian Adults","volume":"99","author":"SA Jongo","year":"2018","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1011051.ref013","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-021-01470-y","article-title":"Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial","volume":"27","author":"M Oneko","year":"2021","journal-title":"Nat Med"},{"key":"ppat.1011051.ref014","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S1473-3099(17)30104-4","article-title":"Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial.","volume":"17","author":"MS Sissoko","year":"2017","journal-title":"Lancet Infect Dis."},{"key":"ppat.1011051.ref015","first-page":"463","article-title":"Malaria Parasites: The Great Escape","volume":"7","author":"L R\u00e9nia","year":"2016","journal-title":"Front Immunol. 2016"},{"key":"ppat.1011051.ref016","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/nm0202-166","article-title":"IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages","volume":"8","author":"LH Carvalho","year":"2002","journal-title":"Nat Med"},{"key":"ppat.1011051.ref017","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.immuni.2016.08.011","article-title":"Liver-Resident Memory CD8(+) T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection","volume":"45","author":"D Fernandez-Ruiz","year":"2016","journal-title":"Immunity"},{"key":"ppat.1011051.ref018","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1126\/science.1241800","article-title":"Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine","volume":"341","author":"RA Seder","year":"2013","journal-title":"Science"},{"key":"ppat.1011051.ref019","doi-asserted-by":"crossref","first-page":"e31247","DOI":"10.1371\/journal.pone.0031247","article-title":"Protective CD8+ T lymphocytes in primates immunized with malaria sporozoites.","volume":"7","author":"WR Weiss","year":"2012","journal-title":"PLoS One."},{"key":"ppat.1011051.ref020","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/nm.4110","article-title":"Protection against malaria at 1 year and immune correlates following PfSPZ vaccination","volume":"22","author":"AS Ishizuka","year":"2016","journal-title":"Nat Med"},{"key":"ppat.1011051.ref021","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.4049\/jimmunol.1700314","article-title":"\u03b3\u03b4 T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations","volume":"199","author":"I Zaidi","year":"2017","journal-title":"J Immunol"},{"key":"ppat.1011051.ref022","doi-asserted-by":"crossref","first-page":"884","DOI":"10.4049\/jimmunol.163.2.884","article-title":"IL-12 and NK cells are required for antigen-specific adaptive immunity against malaria initiated by CD8+ T cells in the Plasmodium yoelii model","volume":"163","author":"DL Doolan","year":"1999","journal-title":"J Immunol"},{"key":"ppat.1011051.ref023","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/pim.12222","article-title":"Batf3 deficiency proves the pivotal role of CD8\u03b1(+) dendritic cells in protection induced by vaccination with attenuated Plasmodium sporozoites","volume":"37","author":"GN Montagna","year":"2015","journal-title":"Parasite Immunol"},{"key":"ppat.1011051.ref024","first-page":"12","article-title":"Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization.","author":"G Moncunill","year":"2020","journal-title":"Sci Transl Med."},{"key":"ppat.1011051.ref025","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41541-020-0196-3","article-title":"Malaria vaccines since 2000: progress, priorities, products.","volume":"5","author":"PE Duffy","year":"2020","journal-title":"NPJ Vaccines."},{"key":"ppat.1011051.ref026","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.3389\/fimmu.2018.02748","article-title":"The Development of Whole Sporozoite Vaccines for Plasmodium falciparum Malaria.","volume":"9","author":"LS Itsara","year":"2018","journal-title":"Front Immunol"},{"key":"ppat.1011051.ref027","doi-asserted-by":"crossref","first-page":"e0233840","DOI":"10.1371\/journal.pone.0233840","article-title":"IMRAS-A clinical trial of mosquito-bite immunization with live, radiation-attenuated P. falciparum sporozoites: Impact of immunization parameters on protective efficacy and generation of a repository of immunologic reagents.","volume":"15","author":"B Hickey","year":"2020","journal-title":"PLoS One."},{"key":"ppat.1011051.ref028","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U A"},{"key":"ppat.1011051.ref029","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection.","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"ppat.1011051.ref030","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/ni.2789","article-title":"Molecular signatures of antibody responses derived from a systems biology study of five human vaccines","volume":"15","author":"S Li","year":"2014","journal-title":"Nat Immunol"},{"key":"ppat.1011051.ref031","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.immuni.2008.05.012","article-title":"A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus","volume":"29","author":"D Chaussabel","year":"2008","journal-title":"Immunity"},{"key":"ppat.1011051.ref032","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis.","volume":"30","author":"A Kr\u00e4mer","year":"2014","journal-title":"Bioinforma Oxf Engl"},{"key":"ppat.1011051.ref033","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1038\/s41467-018-07242-6","article-title":"Leveraging heterogeneity across multiple datasets increases cell-mixture deconvolution accuracy and reduces biological and technical biases.","volume":"9","author":"F Vallania","year":"2018","journal-title":"Nat Commun"},{"key":"ppat.1011051.ref034","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"T Stuart","year":"2019","journal-title":"Cell"},{"key":"ppat.1011051.ref035","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1073\/pnas.1615324114","article-title":"Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection","volume":"114","author":"KE Lyke","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1011051.ref036","first-page":"180","article-title":"Activation of TCR V\u03b41+ and V\u03b41-V\u03b42- \u03b3\u03b4 T Cells upon Controlled Infection with Plasmodium falciparum in Tanzanian Volunteers","volume":"204","author":"T Rutishauser","year":"1950","journal-title":"J Immunol Baltim Md"},{"key":"ppat.1011051.ref037","first-page":"13","article-title":"Repeated Plasmodium falciparum infection in humans drives the clonal expansion of an adaptive \u03b3\u03b4 T cell repertoire","author":"A von Borstel","year":"2021","journal-title":"Sci Transl Med"},{"key":"ppat.1011051.ref038","doi-asserted-by":"crossref","first-page":"e1004894","DOI":"10.1371\/journal.ppat.1004894","article-title":"FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.","volume":"11","author":"RT Sullivan","year":"2015","journal-title":"PLoS Pathog."},{"key":"ppat.1011051.ref039","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.celrep.2014.03.018","article-title":"Interferon-mediated innate immune responses against malaria parasite liver stages","volume":"7","author":"JL Miller","year":"2014","journal-title":"Cell Rep"},{"key":"ppat.1011051.ref040","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.1038\/s41467-019-11819-0","article-title":"Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites","volume":"10","author":"NK Minkah","year":"2019","journal-title":"Nat Commun"},{"key":"ppat.1011051.ref041","doi-asserted-by":"crossref","first-page":"e1010282","DOI":"10.1371\/journal.ppat.1010282","article-title":"Systems analysis of immune responses to attenuated P. falciparum malaria sporozoite vaccination reveals excessive inflammatory signatures correlating with impaired immunity","volume":"18","author":"Y Du","year":"2022","journal-title":"PLoS Pathog"},{"key":"ppat.1011051.ref042","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12936-021-03839-3","article-title":"Early whole blood transcriptional responses to radiation-attenuated Plasmodium falciparum sporozoite vaccination in malaria na\u00efve and malaria pre-exposed adult volunteers","volume":"20","author":"FJ Duffy","year":"2021","journal-title":"Malar J"},{"key":"ppat.1011051.ref043","article-title":"Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection.","author":"FJ Duffy","year":"2022","journal-title":"Infectious Diseases (except HIV\/AIDS);"},{"key":"ppat.1011051.ref044","doi-asserted-by":"crossref","first-page":"14017","DOI":"10.1073\/pnas.0805452105","article-title":"Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria","volume":"105","author":"NW Schmidt","year":"2008","journal-title":"Proc Natl Acad Sci U A"},{"key":"ppat.1011051.ref045","doi-asserted-by":"crossref","first-page":"e1000998","DOI":"10.1371\/journal.ppat.1000998","article-title":"Extreme CD8 T cell requirements for anti-malarial liver-stage immunity following immunization with radiation attenuated sporozoites","volume":"6","author":"NW Schmidt","year":"2010","journal-title":"PLoS Pathog"},{"key":"ppat.1011051.ref046","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1086\/519743","article-title":"Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex Class I-dependent interferon-gamma-producing CD8+ T cells","volume":"196","author":"O Jobe","year":"2007","journal-title":"J Infect Dis"},{"key":"ppat.1011051.ref047","doi-asserted-by":"crossref","first-page":"e36508","DOI":"10.1371\/journal.pone.0036508","article-title":"Long term protection after immunization with P. berghei sporozoites correlates with sustained IFN\u03b3 responses of hepatic CD8+ memory T cells.","volume":"7","author":"K Nganou-Makamdop","year":"2012","journal-title":"PLoS One."},{"key":"ppat.1011051.ref048","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1084\/jem.180.1.353","article-title":"Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells","volume":"180","author":"MC Seguin","year":"1994","journal-title":"J Exp Med"},{"key":"ppat.1011051.ref049","doi-asserted-by":"crossref","first-page":"109956","DOI":"10.1016\/j.celrep.2021.109956","article-title":"Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria","volume":"37","author":"MN Lefebvre","year":"2021","journal-title":"Cell Rep"},{"key":"ppat.1011051.ref050","article-title":"Multi-functional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase I\/IIa trial","author":"L Kurtovic","year":"2020","journal-title":"J Infect Dis"},{"key":"ppat.1011051.ref051","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1038\/s41467-021-21998-4","article-title":"Mechanisms and targets of Fc\u03b3-receptor mediated immunity to malaria sporozoites","volume":"12","author":"G Feng","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1011051.ref052","doi-asserted-by":"crossref","first-page":"e5075","DOI":"10.1371\/journal.pone.0005075","article-title":"Immunization with radiation-attenuated Plasmodium berghei sporozoites induces liver cCD8alpha+DC that activate CD8+T cells against liver-stage malaria.","volume":"4","author":"O Jobe","year":"2009","journal-title":"PloS One."},{"key":"ppat.1011051.ref053","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/1475-2875-13-155","article-title":"Evidence for significant influence of host immunity on changes in differential blood count during malaria","volume":"13","author":"N Berens-Riha","year":"2014","journal-title":"Malar J"},{"key":"ppat.1011051.ref054","first-page":"2","article-title":"Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria","author":"KR Dobbs","year":"2017","journal-title":"JCI Insight"},{"key":"ppat.1011051.ref055","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s12936-017-2108-1","article-title":"Changes in total and differential leukocyte counts during the clinically silent liver phase in a controlled human malaria infection in malaria-na\u00efve Dutch volunteers","volume":"16","author":"ME van Wolfswinkel","year":"2017","journal-title":"Malar J"},{"key":"ppat.1011051.ref056","doi-asserted-by":"crossref","first-page":"e1004393","DOI":"10.1371\/journal.ppat.1004393","article-title":"The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.","volume":"10","author":"LR Antonelli","year":"2014","journal-title":"PLoS Pathog."},{"key":"ppat.1011051.ref057","doi-asserted-by":"crossref","first-page":"e0003978","DOI":"10.1371\/journal.pntd.0003978","article-title":"Transcription Profiling of Malaria-Na\u00efve and Semi-immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge.","volume":"9","author":"ML Rojas-Pe\u00f1a","year":"2015","journal-title":"PLoS Negl Trop Dis."},{"key":"ppat.1011051.ref058","doi-asserted-by":"crossref","first-page":"31291","DOI":"10.1038\/srep31291","article-title":"Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.","volume":"6","author":"TM Tran","year":"2016","journal-title":"Sci Rep"},{"key":"ppat.1011051.ref059","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.4049\/jimmunol.1302669","article-title":"Local immune response to injection of Plasmodium sporozoites into the skin","volume":"193","author":"L Mac-Daniel","year":"2014","journal-title":"J Immunol"},{"key":"ppat.1011051.ref060","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/ni.1953","article-title":"Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses","volume":"11","author":"S Paust","year":"2010","journal-title":"Nat Immunol"},{"key":"ppat.1011051.ref061","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41423-020-0482-z","article-title":"Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria.","volume":"17","author":"S Tukwasibwe","year":"2020","journal-title":"Cell Mol Immunol."},{"key":"ppat.1011051.ref062","doi-asserted-by":"crossref","first-page":"e36806","DOI":"10.7554\/eLife.36806","article-title":"NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity","volume":"7","author":"G Arora","year":"2018","journal-title":"eLife"},{"key":"ppat.1011051.ref063","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2567.2009.03208.x","article-title":"The extensive polymorphism of KIR genes","volume":"129","author":"D Middleton","year":"2010","journal-title":"Immunology"},{"key":"ppat.1011051.ref064","first-page":"7466","article-title":"Heterogeneous human NK cell responses to Plasmodium falciparum-infected erythrocytes","volume":"175","author":"DS Korbel","year":"2005","journal-title":"J Immunol Baltim Md"},{"key":"ppat.1011051.ref065","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41590-021-00911-7","article-title":"Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity","volume":"22","author":"SE de Jong","year":"2021","journal-title":"Nat Immunol"},{"key":"ppat.1011051.ref066","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature21060","article-title":"Sterile protection against human malaria by chemoattenuated PfSPZ vaccine","volume":"542","author":"B Mordm\u00fcller","year":"2017","journal-title":"Nature"},{"key":"ppat.1011051.ref067","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1128\/iai.62.3.855-862.1994","article-title":"Polyclonal expansion of peripheral gamma delta T cells in human Plasmodium falciparum malaria","volume":"62","author":"M Ho","year":"1994","journal-title":"Infect Immun"},{"key":"ppat.1011051.ref068","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.3389\/fmicb.2017.01288","article-title":"A Unique Subset of \u03b3\u03b4 T Cells Expands and Produces IL-10 in Patients with Naturally Acquired Immunity against Falciparum Malaria","volume":"8","author":"T Taniguchi","year":"2017","journal-title":"Front Microbiol"},{"key":"ppat.1011051.ref069","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.immuni.2018.01.009","article-title":"A Macrophage Colony-Stimulating-Factor-Producing \u03b3\u03b4 T Cell Subset Prevents Malarial Parasitemic Recurrence","volume":"48","author":"MR Mamedov","year":"2018","journal-title":"Immunity"},{"key":"ppat.1011051.ref070","doi-asserted-by":"crossref","first-page":"e1002389","DOI":"10.1371\/journal.ppat.1002389","article-title":"Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.","volume":"7","author":"AC Teirlinck","year":"2011","journal-title":"PLoS Pathog."},{"key":"ppat.1011051.ref071","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/375155a0","article-title":"Natural and synthetic non-peptide antigens recognized by human gamma delta T cells","volume":"375","author":"Y Tanaka","year":"1995","journal-title":"Nature"},{"key":"ppat.1011051.ref072","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0014-5793(01)03191-X","article-title":"Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human gammadelta T cells in Escherichia coli.","volume":"509","author":"M Hintz","year":"2001","journal-title":"FEBS Lett"},{"key":"ppat.1011051.ref073","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1126\/science.1068819","article-title":"Adaptive immune response of Vgamma2Vdelta2+ T cells during mycobacterial infections","volume":"295","author":"Y Shen","year":"2002","journal-title":"Science"},{"key":"ppat.1011051.ref074","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.3389\/fimmu.2019.01345","article-title":"Phenotypic Evidence of T Cell Exhaustion and Senescence During Symptomatic Plasmodium falciparum Malaria.","volume":"10","author":"A Frimpong","year":"2019","journal-title":"Front Immunol"},{"key":"ppat.1011051.ref075","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41541-021-00425-1","article-title":"Preimmunization correlates of protection shared across malaria vaccine trials in adults","volume":"7","author":"ML Neal","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ppat.1011051.ref076","first-page":"48","article-title":"Host blood RNA signatures predict the outcome of tuberculosis treatment","volume":"107","author":"EG Thompson","year":"2017","journal-title":"Tuberc Edinb Scotl"},{"key":"ppat.1011051.ref077","doi-asserted-by":"crossref","first-page":"11.14.1","DOI":"10.1002\/0471250953.bi1114s51","article-title":"Mapping RNA-seq Reads with STAR.","volume":"51","author":"A Dobin","year":"2015","journal-title":"Curr Protoc Bioinforma."},{"key":"ppat.1011051.ref078","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data.","volume":"31","author":"S Anders","year":"2015","journal-title":"Bioinforma Oxf Engl"},{"key":"ppat.1011051.ref079","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"DJ McCarthy","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011051.ref080","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/cyto.a.24031","article-title":"OMIP-064: A 27-Color Flow Cytometry Panel to Detect and Characterize Human NK Cells and Other Innate Lymphoid Cell Subsets, MAIT Cells, and \u03b3\u03b4 T Cells.","volume":"97","author":"N Hertoghs","year":"2020","journal-title":"Cytom Part J Int Soc Anal Cytol."},{"key":"ppat.1011051.ref081","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/cyto.a.23331","article-title":"OMIP-044: 28-color immunophenotyping of the human dendritic cell compartment","volume":"93","author":"F Mair","year":"2018","journal-title":"Cytom Part J Int Soc Anal Cytol"},{"key":"ppat.1011051.ref082","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/1471-2105-10-106","article-title":"flowCore: a Bioconductor package for high throughput flow cytometry","volume":"10","author":"F Hahne","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"ppat.1011051.ref083","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"A Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"ppat.1011051.ref084","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Y Hao","year":"2021","journal-title":"Cell"},{"key":"ppat.1011051.ref085","article-title":"glmmSeq: General Linear Mixed Models for Gene-level Differential Expression.","author":"M Lewis","year":"2021","journal-title":"R Package Version 001."},{"key":"ppat.1011051.ref086","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"ppat.1011051.ref087","article-title":"An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation","author":"AA Sergushichev","year":"2016","journal-title":"bioRxiv"},{"key":"ppat.1011051.ref088","author":"J Weiner","year":"2016","journal-title":"tmod: an R package for general and multivariate enrichment analysis"},{"key":"ppat.1011051.ref089","first-page":"144","article-title":"EMPOWERING MULTI-COHORT GENE EXPRESSION ANALYSIS TO INCREASE REPRODUCIBILITY.","volume":"22","author":"WA Haynes","year":"2017","journal-title":"Pac Symp Biocomput Pac Symp Biocomput"},{"key":"ppat.1011051.ref090","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4.","volume":"67","author":"D Bates","year":"2015","journal-title":"J Stat Softw."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011051","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T17:49:14Z","timestamp":1685468954000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011051"}},"subtitle":[],"editor":[{"given":"Ira J.","family":"Blader","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":90,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011051","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1011051","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]}}}