Amphiphysin IIm is required for survival of Chlamydia pneumoniae in macrophages.
Macrophages play a critical role in both innate and acquired immunity because of their unique ability to internalize, kill, and degrade bacterial pathogens through the process of phagocytosis. The adaptor protein, amphiphysin IIm, participates in phagocytosis and is transiently associated with early phagosomes. Certain pathogens, including Chlamydia pneumoniae, have evolved mechanisms to subvert macrophage phagosome maturation and, thus, are able to survive within these cells. We report here that, although amphiphysin IIm is usually only transiently associated with the phagosome, it is indefinitely retained on vacuoles containing C. pneumoniae. Under these wild-type conditions, C. pneumoniae do not elicit significant nitric oxide (NO) production and are not killed. Abrogation of amphiphysin IIm function results in C. pneumoniae-induced NO production and in the sterilization of the vacuole. The data suggest that C. pneumoniae retains amphiphysin IIm on the vacuole to survive within the macrophage.
Gold
Elizabeth S
ES
Institute for Systems Biology, 1441 N. 34th St., Seattle, WA 98103, USA.
Simmons
Randi M
RM
Petersen
Timothy W
TW
Campbell
Lee Ann
LA
Kuo
Cho-Chou
CC
Aderem
Alan
A
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002469:Cell Separation; D002470:Cell Survival; D002690:Chlamydia Infections / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000378:metabolism* / Q000472:pathogenicity; D004247:DNA / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005822:Genetic Vectors; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D009573:Nitrites; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D009419:Nerve Tissue Proteins; D009573:Nitrites; C075637:amphiphysin; D009569:Nitric Oxide; D004247:DNA; D016650:Fluorescein-5-isothiocyanate