Integrin beta 1 regulates phagosome maturation in macrophages through Rac expression.
Phagocytosis and subsequent phagosome maturation by professional phagocytes are essential in the clearance of infectious microbial pathogens. The molecular regulation of phagosome maturation is largely unknown. We show that integrin beta(1) plays critical roles in the phagocytosis of microbial pathogens and phagosome maturation. Macrophages lacking integrin beta(1) expression exhibit reduced phagocytosis of bacteria, including group B streptococcus and Staphylococcus aureus. Furthermore, phagosomes from macrophages lacking integrin beta(1) show lowered maturation rate, defective acquisition of lysosome membrane markers, and reduced F-actin accumulation in the periphagosomal region. Integrin beta(1)-deficient macrophages exhibit impaired bactericidal activity. We found that the expression of the Rho family GTPases Rac1, Rac2, and Cdc42 was reduced in integrin beta(1)-deficient macrophages. Ectopic expression of Rac1, but not Cdc42, in integrin beta(1)-deficient macrophages restored defective phagosome maturation and F-actin accumulation in the periphagosomal region. Importantly, macrophages lacking Rac1/2 also exhibit defective maturation of phagosomes derived from opsonized Escherichia coli or IgG beads. Taken together, these results suggest that integrin beta(1) regulates phagosome maturation in macrophages through Rac expression.
Wang
Qing-Qing
QQ
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Li
Hong
H
Oliver
Tim
T
Glogauer
Michael
M
Guo
Jian
J
He
You-Wen
YW
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D010588:Phagosomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology; D013292:Streptococcus agalactiae / Q000276:immunology; D020744:rac GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein
D019012:Integrin beta1; D009479:Neuropeptides; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C484602:Rac1 protein, mouse