Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates

Aida Valmaseda,Pedro L Alonso,Virander S Chauhan,Christine Langer,Ruth Aguilar,Aina Casellas,Pau Cisteró,Alfredo Mayor,Pedro Aide,Alfons Jiménez,Chetan Chitnis,Quique Bassat,James Beeson,Betuel Sigaúque,Sonia Machevo,Deepak Gaur

doi:10.1038/s41598-017-05025-5

Abstract

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. We hypothesized that anti-parasite immunity acquired upon exposure would limit invasion-related gene (IRG) expression and affect the clinical impact of the infection. 11 IRG transcript levels were measured in P. falciparum isolates by RT-PCR, and IgG/IgM against invasion ligands by Luminex®, in 50 Mozambican adults, 25 children with severe malaria (SM) and 25 with uncomplicated malaria (UM). IRG expression differences among groups and associations between IRG expression and clinical/immunologic parameters were assessed. IRG expression diversity was higher in parasites infecting children than adults (p = 0.022). eba140 and ptramp expression decreased with age (p = 0.003 and 0.007, respectively) whereas p41 expression increased (p = 0.022). pfrh5 reduction in expression was abrupt early in life. Parasite density decreased with increasing pfrh5 expression (p < 0.001) and, only in children, parasite density increased with p41 expression (p = 0.007), and decreased with eba175 (p = 0.013). Antibody responses and IRG expression were not associated. In conclusion, IRG expression is associated with age and parasite density, but not with specific antibody responses in the acute phase of infection. Our results confirm the importance of multi-antigen vaccines development to avoid parasite immune escape when tested in malaria-exposed individuals.

Highlights

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates
All plasma samples from adults and children were tested for specific IgG and IgM levels against the recombinant proteins produced from the studied genes
This is, to our knowledge, the first study to analyze the expression of a wide array of P. falciparum genes involved in invasion among parasite isolates collected from Mozambican individuals covering a broad range of ages, from early infancy to late adulthood

Summary

Introduction

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. The parasites that survive during an infection are thought to express variants corresponding to gaps in the repertoire of host antibodies[24], and variation in invasion ligand use by the parasite during RBC invasion has been shown to mediate evasion of inhibitory antibodies[25, 26] This immune pressure may modulate IRG expression, as it is hypothesized for eba17527, 28, and changes in EBA175 expression and/or use by the parasite alter the susceptibility to acquired inhibitory antibodies[25]. No differences have been found between SM and UM patients in other parasite populations regarding multiplication rates, RBC selectivity, invasion phenotypes[32, 33] or IRG expression levels[18, 28]

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