The inflammatory response induced by Pseudomonas aeruginosa in macrophages enhances apoptotic cell removal
Adriana Valeria Jäger1, Paula Arias2, Maria Virginia Tribulatti2
1Instituto de Investigaciones Biotecnológicas "Dr. R. Ugalde", IIBIO, Universidad Nacional de San Martín (UNSAM), CONICET, B1650HMP, Buenos Aires, Argentina. avjager@gmail.com.
Abstract:
Pathogens phagocytosis and the uptake of apoptotic cells (efferocytosis) are essential macrophages tasks, classically considered as mutually exclusive. Macrophages have been observed to polarize into either pro-inflammatory/microbicidal or anti-inflammatory/efferocytic phenotypes. However, macrophage functions have shown to be more complex. Furthermore, little is known about the regulation of efferocytosis under inflammatory conditions. In this study, we elucidate the modulation of the macrophage efferocytic function during an inflammatory stimulus. We find that bone marrow-derived macrophages (BMDM) are very efficient in engulfing both the bacterial pathogen Pseudomonas aeruginosa and apoptotic cells. BMDM showed a high bactericidal capacity unaffected by the concomitant presence of apoptotic material. Plasticity in macrophage programming, in response to changing environmental cues, may modulate efferocytic capability. In this work, we further show that, after phagocyting and processing Pseudomonas aeruginosa, macrophages highly increase their efferocytic capacity without affecting their phagocytic function. Moreover, we demonstrate that Pseudomonas aeruginosa enhances efferocytosis of these phagocytes through the IL-6 signaling pathway. Our results show that the inflammatory response generated by the bacterial processing enhances these macrophages' capacity to control inflammation through an increased efferocytosis.
Insights
Macrophages can engulf pathogens and apoptotic cells simultaneously. Pseudomonas aeruginosa infection enhances macrophage efferocytosis via IL-6 signaling, improving inflammation control.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages perform phagocytosis (pathogen engulfment) and efferocytosis (apoptotic cell uptake), traditionally viewed as distinct functions.
- Macrophages polarize into pro-inflammatory or anti-inflammatory phenotypes, but their functional plasticity is complex.
- Regulation of efferocytosis during inflammation remains poorly understood.
Purpose of the Study:
- To investigate how inflammatory stimuli modulate macrophage efferocytic function.
- To determine if macrophages can perform phagocytosis and efferocytosis concurrently.
- To elucidate the mechanisms by which bacterial infection influences efferocytosis.
Main Methods:
- Utilized bone marrow-derived macrophages (BMDM) in vitro.
- Exposed BMDM to Pseudomonas aeruginosa and apoptotic cells.
- Analyzed phagocytic and efferocytic capacities.
- Investigated the role of the IL-6 signaling pathway.
Main Results:
- BMDM efficiently phagocytosed Pseudomonas aeruginosa and apoptotic cells concurrently.
- Bactericidal capacity was unaffected by the presence of apoptotic material.
- Post-bacterial processing, macrophages exhibited significantly enhanced efferocytosis without compromising phagocytosis.
- Pseudomonas aeruginosa promoted efferocytosis through the IL-6 signaling pathway.
Conclusions:
- Macrophage functions are more versatile than previously thought, allowing simultaneous pathogen and apoptotic cell clearance.
- Bacterial infection, specifically Pseudomonas aeruginosa, enhances macrophage efferocytic capacity.
- This enhanced efferocytosis, mediated by IL-6 signaling, represents a mechanism for controlling inflammation during infection.
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