ORCID Profile
0000-0003-0366-4112
Current Organisations
Karolinska Universitetssjukhuset
,
Karolinska Institutet
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Publisher: Cold Spring Harbor Laboratory
Date: 03-09-2021
DOI: 10.1101/2021.09.02.458668
Abstract: The mechanism of acquisition and maintenance of natural immunity against Plasmodium falciparum malaria remains unclear. Although, clinical immunity develops over time with repeated malaria episodes, disease tolerance is more rapidly acquired compared to protective immunity. It remains unclear, how pre-existing immune responses impacts the mechanism responsible for disease tolerance. Here, we investigated a cohort of returning travelers treated for acute symptomatic P. falciparum malaria, either infected for the first time, or with a previous history of malaria. Through repeated s ling over one year in a malaria free setting, we were able to study the acute and longitudinal effects of the infection. We combined comprehensive immune cell and plasma protein profiling with integrated and data driven analysis, describing the immune landscape from acute disease to one year after infection. We identified a strong association between pro-inflammatory signatures and γδ T cell expansion. The association was significantly impacted by previous exposure to malaria, resulting in a d ened pro-inflammatory response, which translated to reduced Vδ2 + γδ T cell expansion compared to primary infected in iduals. The d ened inflammatory signal was associated with early expansion of FcγRIII+ monocytes and parasite-specific antibodies of IgG1 and IgG3 isotypes. Our data suggest that the interplay of FcγRIII+ monocytes and a cytophilic parasite-specific IgG during the early blood stage infection lead to lower parasitemia and a d ened pro-inflammatory response with reduced γδ T cell expansion. This enhanced control and reduced inflammation points to a potential mechanism on how tolerance is established following repeated malaria exposure. A systems immunology analysis on natural malaria sheds light on disease tolerance mechanism associated with gamma delta T cell expansion
Publisher: Cold Spring Harbor Laboratory
Date: 08-06-2022
DOI: 10.1101/2022.06.08.495295
Abstract: Many vaccine candidate proteins are under strong selective pressure to ersify in terms of antigenicity. We present a sequencing and data analysis platform for epidemiological surveillance and discovery of indel-rich vaccine antigens by long-read circular consensus sequencing (CCS) in multiclonal pathogen isolates. Our platform uses 40 PCR primers to asymmetrically barcode and identify multiclonal infections in pools of up to 384 s les. We validated the method using 235 mock infections combining 10 synthetic variants of the indel-rich gene merozoite surface protein 2 of Plasmodium falciparum at different concentrations and infection complexities, as well as 95 isolates from P. falciparum -infected residents of Nyamisati, Tanzania. We also constructed a fully automated analysis pipeline that streamlines the processing and interpretation of epidemiological and antigenic ersity data from demultiplexed FASTQ files. This platform can be easily adapted to other polymorphic antigens of interest in Plasmodium and other human pathogens.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.CELREP.2022.110709
Abstract: Natural immunity to malaria develops over time with repeated malaria episodes, but protection against severe malaria and immune regulation limiting immunopathology, called tolerance, develops more rapidly. Here, we comprehensively profile the blood immune system in patients, with or without prior malaria exposure, over 1 year after acute symptomatic Plasmodium falciparum malaria. Using a data-driven analysis approach to describe the immune landscape over time, we show that a d ened inflammatory response is associated with reduced γδ T cell expansion, early expansion of CD16
Location: Switzerland
No related grants have been discovered for David Fernando Plaza.