Characterization of blood dendritic and regulatory T cells in asymptomatic adults with sub-microscopic Plasmodium falciparum or Plasmodium vivax infection.

Zuleima Pava,Kim A Piera,Steven Kho,Jeanne R Poespoprodjo,Tonia Woodberry,Daniel A Lampah,Irene Handayuni,Jutta Marfurt,Enny Kenangalem,Faustina H Burdam,Christian R Engwerda,Andreas Kusuma,Nicholas M Anstey,Gabriela Minigo,Rintis Noviyanti,Ric N Price

doi:10.1186/s12936-016-1382-7

Abstract

BackgroundPlasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease (malaria) and experimental human sub-microscopic infection. Conversely, in asymptomatic microscopy-positive (patent) P. falciparum or P. vivax infection in endemic areas, blood DC increase or retain HLA-DR expression and Treg cells exhibit reduced activation, suggesting that DC and Treg cells contribute to the control of patent asymptomatic infection. The effect of sub-microscopic (sub-patent) asymptomatic Plasmodium infection on DC and Treg cells in malaria-endemic area residents remains unclear.MethodsIn a cross-sectional household survey conducted in Papua, Indonesia, 162 asymptomatic adults were prospectively evaluated for DC and Treg cells using field-based flow cytometry. Of these, 161 individuals (99 %) were assessed retrospectively by polymerase chain reaction (PCR), 19 of whom had sub-microscopic infection with P. falciparum and 15 with sub-microscopic P. vivax infection. Flow cytometric data were re-analysed after re-grouping asymptomatic individuals according to PCR results into negative controls, sub-microscopic and microscopic parasitaemia to examine DC and Treg cell phenotype in sub-microscopic infection.ResultsAsymptomatic adults with sub-microscopic P. falciparum or P. vivax infection had DC HLA-DR expression and Treg cell activation comparable to PCR-negative controls. Sub-microscopic P. falciparum infection was associated with lower peripheral CD4+ T cells and lymphocytes, however sub-microscopic Plasmodium infection had no apparent effect on DC sub-set number or Treg cell frequency.ConclusionsIn contrast to the impairment of DC maturation/function and the activation of Treg cells seen with sub-microscopic parasitaemia in primary experimental human Plasmodium infection, no phenotypic evidence of dysregulation of DC and Treg cells was observed in asymptomatic sub-microscopic Plasmodium infection in Indonesian adults. This is consistent with DC and Treg cells retaining their functional capacity in sub-microscopic asymptomatic infection with P. falciparum or P. vivax in malaria-endemic areas.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1382-7) contains supplementary material, which is available to authorized users.

Highlights

Plasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease and experimental human sub-microscopic infection
The results indicate that while peripheral CD4+ T cells decline, blood DC and Treg cells remain numerically and phenotypically, functionally preserved during asymptomatic sub-microscopic P. falciparum or P. vivax infection
The remainder of 153 asymptomatic adults were included in this analysis, of whom 19 had sub-microscopic P. falciparum infection, 15 had sub-microscopic P. vivax infection, 17 had patent P. falciparum infection, and 19 had patent P. vivax infection

Summary

Introduction

Plasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease (malaria) and experimental human sub-microscopic infection. It is recognized that even in low-transmission settings a large proportion of microscopy-negative individuals have sub-microscopic parasitaemia identified by polymerase chain reaction (PCR) [3,4,5,6,7]. These sub-microscopic infections frequently remain undetected and untreated and contribute significantly to the transmittable reservoir and potentially to morbidity [8]. Sub-microscopic Plasmodium infections are important and warrant consideration in malaria intervention and elimination programmes [9, 13]

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