Interactions of Plasmodium blood and liver stages within a single host
Year: 2010
Type: dissertation
Abstract: In regions of high malaria transmission, infected individuals are constantly exposed to potential re‐infection. Mosquito bites transmit liver‐tropic sporozoites into subjects who already have blood‐stage parasitaemia. How these two stages of the Plasmodium life cycle interact within their host is unknown. Here, using a rodent model, we show ongoing blood stage infections impair the growth of subsequently inoculated sporozoites. Secondary infections are arrested in liver hepatocytes and fail to compete for colonization of red blood cells. This protection of the erythrocyte niche only occurs beyond a certain threshold of blood parasite density, and so is phenotypically akin to quorum sensing. We eliminate Plasmodium‐secreted factors, host cell survival and innate or adaptive immunity as explanations for this observation. Instead, we find parasitized erythrocytes induce expression of the host iron regulatory hormone hepcidin, which by diverting iron from hepatocytes to macrophages, limits Plasmodium growth in the liver. Presuming a similar interaction between malaria and the human host we demonstrate how parasite threshold‐density dependent growth inhibition alone can explain the epidemiological patterns of age‐related risk and complexity of infections in young children. Our findings thus have broad implications for malaria and have general relevance for understanding host‐pathogen interactions.
Author: Sílvia Portugal
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W48433317