title: T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti.
abstract: Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects. Plasma samples were analyzed with a P. falciparum protein microarray, which demonstrated serologic reactivity to 3,877 P. falciparum proteins of known serologic reactivity; however, no antigen-antibody reactions delineating asymptomatics from symptomatics were identified. In contrast, differences in cellular responses were observed. Flow cytometric analysis of patient peripheral blood mononuclear cells co-cultured with P. falciparum infected erythrocytes demonstrated a statistically significant increase in the proportion of T regulatory cells (CD4+ CD25+ CD127-), and increases in unique populations of both NKT-like cells (CD3+ CD8+ CD56+) and CD8mid T cells in asymptomatics compared to symptomatics. Also, CD38+/HLA-DR+ expression on γδ T cells, CD8mid (CD56-) T cells, and CD8mid CD56+ NKT-like cells decreased upon exposure to infected erythrocytes in both groups. Cytometric bead analysis of the co-culture supernatants demonstrated an upregulation of monocyte-activating chemokines/cytokines in asymptomatics, while immunomodulatory soluble factors were elevated in symptomatics. Principal component analysis of these expression values revealed a distinct clustering of individual responses within their respective phenotypic groups. This is the first comprehensive investigation of immune responses to P. falciparum in Haiti, and describes unique cell-mediated immune repertoires that delineate individuals into asymptomatic and symptomatic phenotypes. Future investigations using large scale biological data sets analyzing multiple components of adaptive immunity, could collectively define which cellular responses and molecular correlates of disease outcome are malaria region specific, and which are truly generalizable features of asymptomatic Plasmodium immunity, a research goal of critical priority.
authors.affiliation: Division of Infectious Diseases and Global Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.|Emerging Pathogen Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lehmann
authors.affiliation: Antigen Discovery Inc., Irvine, California, United States of America.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Campo
authors.affiliation: Laboratoire National de Santé Publique (LNSP), Ministère de la Santé Publique et de la Population (MSPP), Port-au-Prince, Haiti.
authors.forename: Micheline
authors.initials: M
authors.lastname: Cicéron
authors.affiliation: Laboratoire National de Santé Publique (LNSP), Ministère de la Santé Publique et de la Population (MSPP), Port-au-Prince, Haiti.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Raccurt
authors.affiliation: Laboratoire National de Santé Publique (LNSP), Ministère de la Santé Publique et de la Population (MSPP), Port-au-Prince, Haiti.
authors.forename: Jacques
authors.identifier: http://orcid.org/0000-0003-0814-5530
authors.initials: J
authors.lastname: Boncy
authors.affiliation: Emerging Pathogen Institute, University of Florida, Gainesville, Florida, United States of America.|Department of Health Services Research, Management and Policy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Valery E M
authors.initials: VE
authors.lastname: Beau De Rochars
authors.affiliation: Division of Infectious Diseases and Global Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.|Emerging Pathogen Institute, University of Florida, Gainesville, Florida, United States of America.|Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Cannella
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000328:Adult; D058345:Asymptomatic Infections / Q000453:epidemiology*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006205:Haiti / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D040081:Protein Array Analysis; D015800:Protozoan Proteins / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018836:Inflammation Mediators; D015800:Protozoan Proteins