Atypical protein kinase C-zeta is essential for delayed phagocytosis of Helicobacter pylori.
Phagocytosis is a rapid actin-dependent endocytic process used by macrophages and neutrophils to ingest and kill microorganisms. Perturbation of phagocytosis is central to the ability of some pathogenic microbes to cause disease, and we demonstrated previously that the ulcerogenic bacterium Helicobacter pylori (Hp) actively retards its uptake by macrophages and subsequently persists inside novel vacuoles called megasomes. Neither the receptor that mediates Hp binding nor the signaling pathways that regulate bacterial engulfment have been defined. Nevertheless, the fact that other phagocytic stimuli do not exhibit delayed phagocytosis suggests that Hp may be ingested by a unique mechanism. We now show that Hp transiently activated protein kinase C (PKC) in macrophages and that atypical PKCzeta and novel PKC(epsilon), but not conventional PKC(alpha), accumulated on forming phagosomes. Pharmacologic agents, isoform-selective pseudosubstrate peptides, and antisense oligonucleotides demonstrated that PKC(zeta) regulated local actin polymerization and bacterial engulfment, whereas other PKC isoforms did not. In contrast, opsonization of Hp with immunoglobulin G (IgG) induced rapid PKC(zeta)-independent uptake and enhanced killing of ingested bacteria. A role for atypical PKCs in phagocytosis has not been described. We conclude that Hp defines a new phagocytic pathway in macrophages that is regulated by PKC(zeta).
Allen
Lee Ann H
LA
Department of Medicine and The Inflammation Program, The University of Iowa and The Veterans Affairs Medical Center, Iowa City, IA 52242, USA. lee-ann-allen@uiowa.edu
Allgood
J Aaron
JA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D004789:Enzyme Activation; D016480:Helicobacter pylori / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology; D010587:Phagocytosis / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D011493:Protein Kinase C; D000099221:Protein Kinase C zeta