Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to ex...

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Autores principales:	Anne C Teirlinck, Matthew B B McCall, Meta Roestenberg, Anja Scholzen, Rob Woestenenk, Quirijn de Mast, Andre J A M van der Ven, Cornelus C Hermsen, Adrian J F Luty, Robert W Sauerwein
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/83476368f6d34b23bbf20116c35efb2a
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spelling	oai:doaj.org-article:83476368f6d34b23bbf20116c35efb2a2021-11-18T06:05:04ZLongevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.1553-73661553-737410.1371/journal.ppat.1002389https://doaj.org/article/83476368f6d34b23bbf20116c35efb2a2011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22144890/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naïve human volunteers undergoing single (n = 5) or multiple (n = 10) experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only 'adaptive' but also 'innate' lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO(+) CD62L(-) effector memory (EM) phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ(+)IL-2(+)) EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P. falciparum, with a persisting contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The implications hereof are positive for malaria vaccine development, but focus attention on those factors potentially inhibiting such responses in the field.Anne C TeirlinckMatthew B B McCallMeta RoestenbergAnja ScholzenRob WoestenenkQuirijn de MastAndre J A M van der VenCornelus C HermsenAdrian J F LutyRobert W SauerweinPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 12, p e1002389 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Anne C Teirlinck Matthew B B McCall Meta Roestenberg Anja Scholzen Rob Woestenenk Quirijn de Mast Andre J A M van der Ven Cornelus C Hermsen Adrian J F Luty Robert W Sauerwein Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.
description	Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naïve human volunteers undergoing single (n = 5) or multiple (n = 10) experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only 'adaptive' but also 'innate' lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO(+) CD62L(-) effector memory (EM) phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ(+)IL-2(+)) EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P. falciparum, with a persisting contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The implications hereof are positive for malaria vaccine development, but focus attention on those factors potentially inhibiting such responses in the field.
format	article
author	Anne C Teirlinck Matthew B B McCall Meta Roestenberg Anja Scholzen Rob Woestenenk Quirijn de Mast Andre J A M van der Ven Cornelus C Hermsen Adrian J F Luty Robert W Sauerwein
author_facet	Anne C Teirlinck Matthew B B McCall Meta Roestenberg Anja Scholzen Rob Woestenenk Quirijn de Mast Andre J A M van der Ven Cornelus C Hermsen Adrian J F Luty Robert W Sauerwein
author_sort	Anne C Teirlinck
title	Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.
title_short	Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.
title_full	Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.
title_fullStr	Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.
title_full_unstemmed	Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.
title_sort	longevity and composition of cellular immune responses following experimental plasmodium falciparum malaria infection in humans.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/83476368f6d34b23bbf20116c35efb2a
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Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

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