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Peer-reviewedCC BY 4.0PLOS One

Macrophages discriminate and sort pathogenic bacteria and apoptotic material during dual-target phagocytosis

  • Celeste Dea1
  • Paula Arias2
  • Sol L. Moroni
  • Nicolás N. Rolandelli
  • Arlinet Kierbel
  1. 1Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
  2. 2Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, Buenos Aires, Argentina
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Abstract

Macrophages are central to immune homeostasis, clearing both pathogens and apoptotic cells. While these processes share some features, they differ functionally: efferocytosis of apoptotic cells is typically anti-inflammatory, whereas bacterial uptake triggers strong inflammatory responses. During infections, both targets may coexist, yet how macrophages handle such complex particles is poorly understood. Previously, we showed that Pseudomonas aeruginosa adheres to apoptotic cells, forming stable composites that can be jointly phagocytosed. Here, using quantitative confocal and live-cell imaging, we investigate how macrophages engage and internalize these dual targets. We find that macrophages employ distinct strategies depending on target composition. Apoptotic cells alone are engulfed intact within tight, actin-rich membrane cups, whereas bacteria-laden apoptotic cells induce protrusive, actin-driven extensions that navigate along the apoptotic scaffold to access bacteria. Individual bacteria are selectively extracted and internalized, while apoptotic material is internalized in a piecemeal manner. Early phagosome analysis shows that most contain either bacteria or apoptotic material alone, with mixed cargo being less frequent. These findings demonstrate that macrophages can discriminate and sort the components of complex targets during uptake. This work provides a framework for understanding how innate immune cells integrate pathogen clearance while managing apoptotic material.

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Cite

BibTeXRIS
BibTeX
@article{dea2026macrophages,
  title = {{Macrophages discriminate and sort pathogenic bacteria and apoptotic material during dual-target phagocytosis}},
  author = {Celeste Dea and Paula Arias and Sol L. Moroni and Nicolás N. Rolandelli and Arlinet Kierbel},
  journal = {PLOS One},
  year = {2026},
  month = oct,
  doi = {10.1371/journal.pone.0356679},
  url = {https://doi.org/10.1371/journal.pone.0356679},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Macrophages discriminate and sort pathogenic bacteria and apoptotic material during dual-target phagocytosis
AU  - Celeste Dea
AU  - Paula Arias
AU  - Sol L. Moroni
AU  - Nicolás N. Rolandelli
AU  - Arlinet Kierbel
PY  - 2026
DA  - 2026/10/07
JO  - PLOS One
DO  - 10.1371/journal.pone.0356679
UR  - https://doi.org/10.1371/journal.pone.0356679
AB  - Macrophages are central to immune homeostasis, clearing both pathogens and apoptotic cells. While these processes share some features, they differ functionally: efferocytosis of apoptotic cells is typically anti-inflammatory, whereas bacterial uptake triggers strong inflammatory responses. During infections, both targets may coexist, yet how macrophages handle such complex particles is poorly understood. Previously, we showed that Pseudomonas aeruginosa adheres to apoptotic cells, forming stable composites that can be jointly phagocytosed. Here, using quantitative confocal and live-cell imaging, we investigate how macrophages engage and internalize these dual targets. We find that macrophages employ distinct strategies depending on target composition. Apoptotic cells alone are engulfed intact within tight, actin-rich membrane cups, whereas bacteria-laden apoptotic cells induce protrusive, actin-driven extensions that navigate along the apoptotic scaffold to access bacteria. Individual bacteria are selectively extracted and internalized, while apoptotic material is internalized in a piecemeal manner. Early phagosome analysis shows that most contain either bacteria or apoptotic material alone, with mixed cargo being less frequent. These findings demonstrate that macrophages can discriminate and sort the components of complex targets during uptake. This work provides a framework for understanding how innate immune cells integrate pathogen clearance while managing apoptotic material.
SN  - 1932-6203
ER  -