Circadian Regulation of Leishmania Parasite Internalisation in Macrophages and Downstream Cellular Events
ABSTRACT Leishmania spp. parasites use macrophages as a host cell during infection. As a result, macrophages have a dual role: clearing the parasite as well as acting as host cells. Recently, studies have shown that macrophages harbour circadian clocks, which affect many of their functions such as p...
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Published in | Parasite immunology Vol. 46; no. 6; pp. e13053 - n/a |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.06.2024
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Subjects | |
Online Access | Get full text |
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Summary: | ABSTRACT
Leishmania spp. parasites use macrophages as a host cell during infection. As a result, macrophages have a dual role: clearing the parasite as well as acting as host cells. Recently, studies have shown that macrophages harbour circadian clocks, which affect many of their functions such as phagocytosis, receptor expression and cytokine release. Interestingly, Leishmania major infection in hosts was also shown to be under circadian control. Therefore, we decided to investigate what underlies the rhythms of L. major infection within macrophages. Using a culture model of infection of bone marrow–derived macrophages with L. major promastigotes, we show that the parasites are internalised into macrophages with a 24‐h variation dependent on a functional circadian clock in the cells. This was associated with a variation in the number of parasites per macrophage. The cell surface expression of parasite receptors was not controlled by the cells' circadian clock. In contrast, the expression of the components of the endocytic pathway, EEA1 and LC3b, varied according to the time of infection. This was paralleled by variations in parasite‐induced ROS production as well as cytokine tumour necrosis factor α. In summary, we have uncovered a time‐dependent regulation of the internalisation of L. major promastigotes in macrophages, controlled by the circadian clock in these cells, as well as subsequent cellular events in the endocytic pathway, intracellular signalling and cytokine production. |
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Bibliography: | This project was funded by grants from the Canadian Institutes of Health Research (PJT‐168847, to N.C. and M.O.; MOP‐119322, to N.C.) and Douglas Institute Foundation, doctoral fellowships from McGill University Faculty of Medicine and Health Sciences and Fonds de Recherche du Québec—Santé (to P.C.C.), and a Canada Graduate Scholarship—Master's (to S.K.S.). Funding The first two authors contributed equally to this manuscript. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0141-9838 1365-3024 |
DOI: | 10.1111/pim.13053 |