Monocytes, particularly nonclassical ones, lose their opsonic and nonopsonic phagocytosis capacity during pediatric cerebral malaria
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Published on: July 17, 2014
Bertin Vianou1,2, Jade Royo1, Sébastien Dechavanne3
1UMR152 PHARMADEV, IRD, UPS, Toulouse University, Toulouse, France.
Introduction:
Innate immunity is crucial to reducing parasite burden and contributing to survival in severe malaria. Monocytes are key actors in the innate response and, like macrophages, are plastic cells whose function and phenotype are regulated by the signals from the microenvironment. In the context of cerebral malaria (CM), monocyte response constitutes an important issue to understand. We previously demonstrated that decreased percentages of nonclassical monocytes were associated with death outcomes in CM children. In the current study, we postulated that monocyte phagocytosis function is impacted by the severity of malaria infection.
Methods:
To study this hypothesis, we compared the opsonic and nonopsonic phagocytosis capacity of circulant monocytes from Beninese children with uncomplicated malaria (UM) and CM. For the CM group, samples were obtained at inclusion (D0) and 3 and 30 days after treatment (D3, D30). The phagocytosis capacity of monocytes and their subsets was characterized by flow cytometry and transcriptional profiling by studying genes known for their functional implication in infected-red blood cell (iRBC) elimination or immune escape.
Results:
Our results confirm our hypothesis and highlight the higher capacity of nonclassical monocytes to phagocyte iRBC. We also confirm that a low number of nonclassical monocytes is associated with CM outcome when compared to UM, suggesting a mobilization of this subpopulation to the cerebral inflammatory site. Finally, our results suggest the implication of the inhibitory receptors LILRB1, LILRB2, and Tim3 in phagocytosis control.
Discussion:
Taken together, these data provide a better understanding of the interplay between monocytes and malaria infection in the pathogenicity of CM.
Insights
In severe malaria, nonclassical monocytes show a higher capacity to phagocytose infected red blood cells. Lower counts of these monocytes correlate with cerebral malaria outcomes, suggesting their role in the brain's inflammatory response.
Area of Science:
- Immunology
- Infectious Diseases
- Pathophysiology
Background:
- Innate immunity is vital for controlling parasite load and survival in severe malaria.
- Monocytes, key innate immune cells, are plastic and their functions are influenced by the microenvironment.
- Understanding monocyte responses is crucial for cerebral malaria (CM) pathogenesis.
Purpose of the Study:
- To investigate the impact of malaria severity on monocyte phagocytosis function.
- To compare the phagocytosis capacity of monocytes in uncomplicated malaria (UM) versus CM.
- To identify monocyte subsets and molecular mechanisms involved in clearing infected red blood cells (iRBCs).
Main Methods:
- Compared phagocytosis capacity (opsonic and nonopsonic) of monocytes from children with UM and CM.
- Analyzed monocyte subsets and gene expression related to iRBC elimination and immune escape.
- Collected samples from CM patients at diagnosis (D0), and 3 (D3) and 30 (D30) days post-treatment.
Main Results:
- Nonclassical monocytes demonstrated a higher capacity for phagocytosing iRBCs.
- Lower percentages of nonclassical monocytes were associated with CM outcomes compared to UM.
- Inhibitory receptors LILRB1, LILRB2, and Tim-3 were implicated in regulating phagocytosis.
Conclusions:
- Monocyte phagocytosis function is significantly impacted by malaria severity.
- Nonclassical monocytes play a key role in clearing iRBCs, and their depletion is linked to CM.
- These findings enhance understanding of monocyte-macrophage interactions in CM pathogenesis.
