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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1171176/full |
| _version_ | 1797743395736649728 |
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| author | Alejandra Herbert Mainero Philip J. Spence Sarah E. Reece Sarah E. Reece Tsukushi Kamiya Tsukushi Kamiya Tsukushi Kamiya |
| author_facet | Alejandra Herbert Mainero Philip J. Spence Sarah E. Reece Sarah E. Reece Tsukushi Kamiya Tsukushi Kamiya Tsukushi Kamiya |
| author_sort | Alejandra Herbert Mainero |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T14:54:53Z |
| format | Article |
| id | doaj.art-ab390f5c1f1a44ecb8245a89ac571f72 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T14:54:53Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ab390f5c1f1a44ecb8245a89ac571f722023-08-15T04:17:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.11711761171176The impact of innate immunity on malaria parasite infection dynamics in rodent modelsAlejandra Herbert Mainero0Philip J. Spence1Sarah E. Reece2Sarah E. Reece3Tsukushi Kamiya4Tsukushi Kamiya5Tsukushi Kamiya6Institute of Ecology and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomInstitute of Ecology and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomInstitute of Ecology and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomCentre for Interdisciplinary Research in Biology, Collège de France, Paris, FranceHRB, National University of Ireland Galway, Galway, IrelandDecades 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1171176/fullplasmodiummeta-analysiswithin-host dynamicsinnate immunityrodent malaria |
| spellingShingle | Alejandra Herbert Mainero Philip J. Spence Sarah E. Reece Sarah E. Reece Tsukushi Kamiya Tsukushi Kamiya Tsukushi Kamiya The impact of innate immunity on malaria parasite infection dynamics in rodent models Frontiers in Immunology plasmodium meta-analysis within-host dynamics innate immunity rodent malaria |
| 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 | plasmodium meta-analysis within-host dynamics innate immunity rodent malaria |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1171176/full |
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