Phagocytosis of bacteria is enhanced in macrophages undergoing nutrient deprivation.
Phagocytosis represents a mechanism used by macrophages to remove pathogens and cellular debris. Recent evidence suggests that phagocytosis is stimulated under specific conditions of stress, such as extracellular pressure and hypoxia. In the present study, we show that amino acid or glucose deprivation caused an increase in the phagocytosis of heat-inactivated Escherichia coli and Staphylococcus aureus by macrophages, but not the uptake of platelets, apoptotic cells or beads. Increased phagocytosis of bacteria could be blocked by phagocytosis inhibitors and was found to be dependent on p38 mitogen-activated protein kinase activity and scavenger receptor A. Although nutrient deprivation is a strong stimulus of autophagy, autophagosome formation was not critical for the uptake of bacteria because phagocytic clearance was not inhibited after down-regulation of the autophagy essential gene Atg7. Moreover, enhanced uptake of bacteria should not be considered as a general stress response because phagocytosis of bacteria was not stimulated after exposure of macrophages to the genotoxic agent camptothecin, heat (40 degrees C) or thapsigargin-induced endoplasmic reticulum stress. Overall, the results obtained in the present study indicate that nutrient deprivation can stimulate macrophages to fight bacterial infections.
Martinet
Wim
W
Division of Pharmacology, University of Antwerp, Antwerp, Belgium. wim.martinet@ua.ac.be
Schrijvers
Dorien M
DM
Timmermans
Jean-Pierre
JP
Herman
Arnold G
AG
De Meyer
Guido R Y
GR
D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000502:physiology*; D051116:Receptors, Scavenger / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism*
D051116:Receptors, Scavenger; D049452:Green Fluorescent Proteins