Linking functional and molecular mechanisms of host resilience to malaria infection.
Elife
; 102021 10 12.
Article
em En
| MEDLINE
| ID: mdl-34636723
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmodium chabaudi
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Eritrócitos
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Malária
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article