Zipper Mechanism Ingestion occurs by sequential engagement of

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.

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

Salmonellosis Factors for disease: Pathogen – Virulence? Host – Immune function? Environment – Dose? http: //www. worldwidevaccines. com/typhoid_4. jpg

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.

SIGNALS FROM OUTSIDE • How to invade non-phagocytic cells? • SPI-1 TTSS: – Activate regulators Cdc 42 and Rac 1 in host. – Bacteria-host interaction to promote polymerization and bundling of actin filaments. – Restore normal actin dynamics after invasion.

MEMBRANE RUFFLING Ruffles, Macropinocytosis, Engulfment: – Sop B, E, E 2 activate GTPases Cdc 42, Rac 1. – Activate WASP, Scar/Wave, Arp 2/3 to initiate actin polymerization. – Translocate: • Sip. C – Insert in target cell membrane, direct filament formation at sites adjacent to bacteria? • Sip. A – ‘Molecular staple’ to stabilize actin filaments. • Spt. P – Reverse cytoskeletal rearrangements.

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

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

Does all this talk of phagocytosis make you hungry? The End http: //www. sph. tulane. edu/%7 Edmsander/WWW/Video/Macmov. html