2. Zipper Mechanism
Ingestion occurs by sequential engagement of the phagocyte membrane with the particle surface. Pseudopod advance proceeds no further than the receptor-ligand interaction permits.

3. TRIGGER MECHANISM
Particle binding initiates an ‘all or none’ phagocytic response.

8. Salmonellosis Factors for disease: Pathogen – Virulence?
Host – Immune function?
Environment – Dose?

9. Salmonella Virulence
SPI-1: TTSS to deliver effector proteins to cytoplasm that induce cytoskeletal rearrangments to facilitate Salmonella uptake in SCV.
SPI-2: TTSS to deliver effector proteins from SCV to cell cytoplasm that induce focal actin condensation around SCV.
spv: prevents actin polymerization needed for F-actin filament formation.

11. SIGNALS FROM OUTSIDE How to invade non-phagocytic cells? SPI-1 TTSS:
Activate regulators Cdc42 and Rac1 in host.
Bacteria-host interaction to promote polymerization and bundling of actin filaments.
Restore normal actin dynamics after invasion.

12. MEMBRANE RUFFLING Ruffles, Macropinocytosis, Engulfment:
Sop B, E, E2 activate GTPases Cdc42, Rac1.
Activate WASP, Scar/Wave, Arp2/3 to initiate actin polymerization.
Translocate:
SipC – Insert in target cell membrane, direct filament formation at sites adjacent to bacteria?
SipA – ‘Molecular staple’ to stabilize actin filaments.
SptP – Reverse cytoskeletal rearrangements.

13. SIGNALS FROM INSIDE How to proliferate within cells? SPI-2 TTSS: SpvB:
Translocate effectors from SCV to cytoplasm:
Form filamentous endosomes
Decrease recruitment of NADPH oxidase
Change SCV fusion pathway
VAP formation of actin around SCV
SpvB:
Depolymerizes actin from F filaments to G monomers with ADP ribosylation.

17. TIMING IS EVERYTHING Events are carefully orchestrated:
Focal actin polymerization for cell invasion.
Caused by SPI-1 effectors
Reversed by SptP
Focal actin condensation for effects from SCV.
Caused by SPI-2 effectors
Reversed by SpvB
Depolymerization leads to apoptosis and further Salmonella phagocytosis!

19. Does all this talk of phagocytosis make you hungry?
The End