Linking Functional and Molecular Mechanisms of Host Resilience to Malaria Infection

Overview

Journal Elife

Specialty Biology

Date 2021 Oct 12

PMID 34636723

Citations 4

Authors

Tsukushi Kamiya

Nicole M Davis

Megan A Greischar

David Schneider

Nicole Mideo

Affiliations

Soon will be listed here.

Abstract

It remains challenging to understand why some hosts suffer severe illnesses, while others are unscathed by the same infection. We fitted a mathematical model to longitudinal measurements of parasite and red blood cell density in murine hosts from diverse genetic backgrounds to identify aspects of within-host interactions that explain variation in host resilience and survival during acute malaria infection. Among eight mouse strains that collectively span 90% of the common genetic diversity of laboratory mice, we found that high host mortality was associated with either weak parasite clearance, or a strong, yet imprecise response that inadvertently removes uninfected cells in excess. Subsequent cross-sectional cytokine assays revealed that the two distinct functional mechanisms of poor survival were underpinned by low expression of either pro- or anti-inflammatory cytokines, respectively. By combining mathematical modelling and molecular immunology assays, our study uncovered proximate mechanisms of diverse infection outcomes across multiple host strains and biological scales.

Citing Articles

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

Herbert Mainero A, Spence P, Reece S, Kamiya T Front Immunol. 2023; 14:1171176.

PMID: 37646037 PMC: 10461630. DOI: 10.3389/fimmu.2023.1171176.

Rapid adaptation to a novel pathogen through disease tolerance in a wild songbird.

Henschen A, Vinkler M, Langager M, Rowley A, Dalloul R, Hawley D PLoS Pathog. 2023; 19(6):e1011408.

PMID: 37294834 PMC: 10287013. DOI: 10.1371/journal.ppat.1011408.

Targeting malaria parasites inside mosquitoes: ecoevolutionary consequences.

Kamiya T, Paton D, Catteruccia F, Reece S Trends Parasitol. 2022; 38(12):1031-1040.

PMID: 36209032 PMC: 9815470. DOI: 10.1016/j.pt.2022.09.004.

Using the Collaborative Cross and Diversity Outbred Mice in Immunology.

Hackett J, Gibson H, Frelinger J, Buntzman A Curr Protoc. 2022; 2(9):e547.

PMID: 36066328 PMC: 9612550. DOI: 10.1002/cpz1.547.

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