Perkinsus marinus suppresses in vitro eastern oyster apoptosis via IAP-dependent and caspase-independent pathways involving TNFR, NF-kB, and oxidative pathway crosstalk

• Published in: Developmental and comparative immunology 2022-04, Vol.129, p.104339, Article 104339
• Main Authors: Witkop, Erin M., Wikfors, Gary H., Proestou, Dina A., Lundgren, Kathryn Markey, Sullivan, Mary, Gomez-Chiarri, Marta
• Format: Article
• Language: English
• Subjects: Amino Acid Chloromethyl Ketones; Animals; Apicomplexa; Apoptosis; Caspase; Caspase inhibitors; Caspases; Crassostrea - parasitology; Crassostrea virginica; Crosstalk; Dermo disease; Differential expression; Hemocytes; Hemocytes - parasitology; Host-Parasite Interactions; Hydrolase; IAP; IAP protein; Incubation; Inhibitor of Apoptosis Proteins; Kinases; Leukocytes (granulocytic); Mitochondria; NF-kappa B; NF-κB protein; Oxidation; Oxidation-Reduction; Oxidation-reduction potential; Oxidative Stress; Oyster; Oysters; Parasites; Perkinsus marinus; Tumor necrosis factor receptors; WGCNA
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2022.104339

The protozoan parasite Perkinsus marinus causes Dermo disease in eastern oysters, Crassostrea virginica, and can suppress apoptosis of infected hemocytes using incompletely understood mechanisms. This study challenged hemocytes in vitro with P. marinus for 1 h in the presence or absence of caspase inhibitor Z-VAD-FMK or Inhibitor of Apoptosis protein (IAP) inhibitor GDC-0152. Hemocytes exposure to P. marinus significantly reduced granulocyte apoptosis, and pre-incubation with Z-VAD-FMK did not affect P. marinus-induced apoptosis suppression. Hemocyte pre-incubation with GDC-0152 prior to P. marinus challenge further reduced apoptosis of granulocytes with engulfed parasite, but not mitochondrial permeabilization. This suggests P. marinus-induced apoptosis suppression may be caspase-independent, affect an IAP-involved pathway, and occur downstream of mitochondrial permeabilization. P. marinus challenge stimulated hemocyte differential expression of oxidation-reduction, TNFR, and NF-kB pathways. WGCNA analysis of P. marinus expression in response to hemocyte exposure revealed correlated protease, kinase, and hydrolase expression that could contribute to P. marinus-induced apoptosis suppression. •Basal hemocyte apoptosis in oysters may be IAP-dependent.•P. marinus suppression of apoptosis may involve caspase-independent pathways.•P. marinus suppressed apoptosis downstream or independently of mitochondrial permeabilization.•Hemocyte apoptosis suppression involved oxidation-reduction, TNFR, NF-kB pathways.•P. marinus enzymes potentially involved in apoptosis suppression were identified.