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The impact of innate immunity on malaria parasite infection dynamics in rodent models

Decades of research have probed the molecular and cellular mechanisms that control the immune response to malaria. Yet many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to seek consen...

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Autores principales: Herbert Mainero, Alejandra, Spence, Philip J., Reece, Sarah E., Kamiya, Tsukushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461630/
https://www.ncbi.nlm.nih.gov/pubmed/37646037
http://dx.doi.org/10.3389/fimmu.2023.1171176
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author Herbert Mainero, Alejandra
Spence, Philip J.
Reece, Sarah E.
Kamiya, Tsukushi
author_facet Herbert Mainero, Alejandra
Spence, Philip J.
Reece, Sarah E.
Kamiya, Tsukushi
author_sort Herbert Mainero, Alejandra
collection PubMed
description Decades of research have probed the molecular and cellular mechanisms that control the immune response to malaria. Yet many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to seek consensus on the effect of innate immunity on parasite replication, examining three different species of rodent malaria parasite. Screening published studies that span four decades of research we collate, curate, and statistically analyze infection dynamics in immune-deficient or -augmented mice to identify and quantify general trends and reveal sources of disagreement among studies. Additionally, we estimate whether host factors or experimental methodology shape the impact of immune perturbations on parasite burden. First, we detected meta-analytic mean effect sizes (absolute Cohen’s h) for the difference in parasite burden between treatment and control groups ranging from 0.1475 to 0.2321 across parasite species. This range is considered a small effect size and translates to a modest change in parasitaemia of roughly 7-12% on average at the peak of infection. Second, we reveal that variation across studies using P. chabaudi or P. yoelii is best explained by stochasticity (due to small sample sizes) rather than by host factors or experimental design. Third, we find that for P. berghei the impact of immune perturbation is increased when young or female mice are used and is greatest when effector molecules (as opposed to upstream signalling molecules) are disrupted (up to an 18% difference in peak parasitaemia). Finally, we find little evidence of publication bias suggesting that our results are robust. The small effect sizes we observe, across three parasite species, following experimental perturbations of the innate immune system may be explained by redundancy in a complex biological system or by incomplete (or inappropriate) data reporting for meta-analysis. Alternatively, our findings might indicate a need to re-evaluate the efficiency with which innate immunity controls parasite replication early in infection. Testing these hypotheses is necessary to translate understanding from model systems to human malaria.
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spelling pubmed-104616302023-08-29 The impact of innate immunity on malaria parasite infection dynamics in rodent models Herbert Mainero, Alejandra Spence, Philip J. Reece, Sarah E. Kamiya, Tsukushi Front Immunol Immunology Decades of research have probed the molecular and cellular mechanisms that control the immune response to malaria. Yet many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to seek consensus on the effect of innate immunity on parasite replication, examining three different species of rodent malaria parasite. Screening published studies that span four decades of research we collate, curate, and statistically analyze infection dynamics in immune-deficient or -augmented mice to identify and quantify general trends and reveal sources of disagreement among studies. Additionally, we estimate whether host factors or experimental methodology shape the impact of immune perturbations on parasite burden. First, we detected meta-analytic mean effect sizes (absolute Cohen’s h) for the difference in parasite burden between treatment and control groups ranging from 0.1475 to 0.2321 across parasite species. This range is considered a small effect size and translates to a modest change in parasitaemia of roughly 7-12% on average at the peak of infection. Second, we reveal that variation across studies using P. chabaudi or P. yoelii is best explained by stochasticity (due to small sample sizes) rather than by host factors or experimental design. Third, we find that for P. berghei the impact of immune perturbation is increased when young or female mice are used and is greatest when effector molecules (as opposed to upstream signalling molecules) are disrupted (up to an 18% difference in peak parasitaemia). Finally, we find little evidence of publication bias suggesting that our results are robust. The small effect sizes we observe, across three parasite species, following experimental perturbations of the innate immune system may be explained by redundancy in a complex biological system or by incomplete (or inappropriate) data reporting for meta-analysis. Alternatively, our findings might indicate a need to re-evaluate the efficiency with which innate immunity controls parasite replication early in infection. Testing these hypotheses is necessary to translate understanding from model systems to human malaria. Frontiers Media S.A. 2023-08-14 /pmc/articles/PMC10461630/ /pubmed/37646037 http://dx.doi.org/10.3389/fimmu.2023.1171176 Text en Copyright © 2023 Herbert Mainero, Spence, Reece and Kamiya https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Herbert Mainero, Alejandra
Spence, Philip J.
Reece, Sarah E.
Kamiya, Tsukushi
The impact of innate immunity on malaria parasite infection dynamics in rodent models
title The impact of innate immunity on malaria parasite infection dynamics in rodent models
title_full The impact of innate immunity on malaria parasite infection dynamics in rodent models
title_fullStr The impact of innate immunity on malaria parasite infection dynamics in rodent models
title_full_unstemmed The impact of innate immunity on malaria parasite infection dynamics in rodent models
title_short The impact of innate immunity on malaria parasite infection dynamics in rodent models
title_sort impact of innate immunity on malaria parasite infection dynamics in rodent models
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461630/
https://www.ncbi.nlm.nih.gov/pubmed/37646037
http://dx.doi.org/10.3389/fimmu.2023.1171176
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