AUTHOR=Donsante Samantha , Siciliano Giulia , Ciardo Mariagrazia , Palmisano Biagio , Messina Valeria , de Turris Valeria , Farinacci Giorgia , Serafini Marta , Silvestrini Francesco , Corsi Alessandro , Riminucci Mara , Alano Pietro 

TITLE=An in vivo humanized model to study homing and sequestration of Plasmodium falciparum transmission stages in the bone marrow

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1161669

DOI=10.3389/fcimb.2023.1161669

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>Recent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of <italic>P. falciparum</italic> malaria by providing a “niche” for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized <italic>in vivo</italic> models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.</p></sec><sec><title>Methods</title><p>We report a novel experimental system based on the infusion of immature <italic>P. falciparum</italic> gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.</p></sec><sec><title>Results</title><p>We demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.</p></sec><sec><title>Discussion</title><p>Our model represents a powerful tool to study BM function and the interplay essential for parasite transmission in <italic>P. falciparum</italic> malaria and can be extended to study other infections in which the human BM plays a role.</p></sec>