Abstract
Motility factors are fundamental for parasite invasion, migration, proliferation and immune evasion and thus can influence parasitic disease pathogenesis and virulence. Salmonid enteronecrosis is caused by a myxozoan (Phylum Cnidarian) parasite, Ceratonova shasta. Three parasite genotypes (0, I, II) occur, with varying degrees of virulence in its host, making it a good model for examining the role of motility in virulence. We compare C. shasta cell motility between genotypes and describe how the cellular protrusions interact with the host. We support these observations with motility gene expression analyses. C. shasta stages can move by single or combined used of filopodia, lamellipodia and blebs, with different behaviors such as static adhesion, crawling or blebbing, some previously unobserved in myxozoans. C. shasta stages showed high flexibility of switching between different morphotypes, suggesting a high capacity to adapt to their microenvironment. Exposure to fibronectin showed that C. shasta stages have extraordinary adhesive affinities to glycoprotein components of the extracellular matrix (ECM). When comparing C. shasta genotypes 0 (low virulence, no mortality) and IIR (high virulence, high mortality) infections in rainbow trout, major differences were observed with regard to their migration to the target organ, gene expression patterns and proliferation rate in the host. IIR is characterized by rapid multiplication and fast amoeboid bleb-based migration to the gut, where adhesion (mediated by integrin-β and talin), ECM disruption and virulent systemic dispersion of the parasite causes massive pathology. Genotype 0 is characterized by low proliferation rates, slow directional and early adhesive migration and localized, non-destructive development in the gut. We conclude that parasite adhesion drives virulence in C. shasta and that effectors, such as integrins, reveal themselves as attractive therapeutic targets in a group of parasites for which no effective treatments are known.
Highlights
The capacity of movement is fundamental for cells, and most of them rely on a functionally conserved actomyosin cytoskeleton system that allows spatial displacement
Three main types of cell protrusions were observed on the outer, or primary, cell of infected with the most virulent genotype (IIR) C. shasta stages: blebs, filopodia and lamellipodia. These cell protrusions were associated with different behaviors: (a) blebbing-driven movement with little to moderate displacement and low adhesion; and (b) lamellipodia-driven movement with high adhesion
We demonstrate that C. shasta filopodia and lamellipodia have very strong affinity for glycoprotein components of the extracellular matrix (ECM), such as fibronectin
Summary
The capacity of movement is fundamental for cells, and most of them rely on a functionally conserved actomyosin cytoskeleton system that allows spatial displacement. The ability to switch plastically between different motility modes and cell protrusions depending on the environment optimizes cell migration. Single cell motility depends on the physical properties of the extracellular matrix (ECM), extracellular proteolysis and signaling factors. Two main modes of migration, i.e., mesenchymal vs amoeboid can be distinguished by their leading edge structure, cell shape, and the degree of cell adhesion to the ECM. Mesenchymal migration is characterized by polarized and elongated cells that display actin-rich cell protrusions (lamellipodia/sheet-like protrusions and lobopodia), high integrin-mediated adhesion, and proteolysis of the ECM. Amoeboid migration is distinguished by round cells with low or no adhesion that can deform to move cross the ECM without proteolysis, using blebs, pseudopodia and filopodia [1,2,3]
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