T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

• Published in: PloS one Vol. 12; no. 4; p. e0174718
• Main Authors: Lehmann, Jason S., Campo, Joseph J., Cicéron, Micheline, Raccurt, Christian P., Boncy, Jacques, Beau De Rochars, Valery E. M., Cannella, Anthony P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.04.2017; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Adaptive Immunity - immunology; Adolescent; Adult; Analysis; Arthritis; Asymptomatic Infections - epidemiology; Biology and Life Sciences; Care and treatment; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - immunology; Chemokines; Cross-Sectional Studies; Cytokines; Erythrocytes; Erythrocytes - parasitology; Female; Growth factors; Haiti - epidemiology; Human populations; Humans; Immune response; Immunoglobulin G - immunology; Immunoglobulin M - immunology; Immunology; Infections; Infectious diseases; Inflammation; Inflammation - immunology; Inflammation Mediators - metabolism; Lymphocytes T; Malaria; Malaria, Falciparum - epidemiology; Malaria, Falciparum - immunology; Malaria, Falciparum - parasitology; Male; Medicine; Medicine and Health Sciences; Microscopy; Middle Aged; Monocytes; Parasites; Pathogens; People and places; Physiological aspects; Plasmodium falciparum; Plasmodium falciparum - immunology; Population; Principal components analysis; Protein Array Analysis; Protozoan Proteins - immunology; Public health; Recall; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Vector-borne diseases; Young Adult; Haiti; Florida; United States > US; Port Au Prince Haiti
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174718

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.