Comparison of Macrophage Antimicrobial Responses Induced by Type II Interferons of the Goldfish (Carassius auratus L.)

Abstract

Unlike mammals, bony fish have two type II interferons, IFN␥ and IFN␥rel, whose pro-inflammatory functions have not been fully characterized. To elucidate the distinct roles of these type II interferons of bony fish, we examined the effects of recombinant goldfish (rg) IFN␥ and IFN␥rel on the macrophage antimicrobial responses, immune gene expression, and their signaling pathways. Our findings indicate that rgIFN␥ and rgIFN␥rel possess unique capacities to mediate each of the above processes. Q-PCR analysis revealed similar expression of both cytokines in tissues and immune cell populations of the goldfish, although IFN␥ mRNA levels were generally higher in most tissues and cell types. Whereas rgIFN␥ had long-lasting effects on the priming of goldfish monocyte ROI production, the rgIFN␥rel had relatively short-lived ROI priming potential and eventually down-regulated the priming of ROI production induced by rgIFN␥ or rgTNF␣2. Whereas rgIFN␥ induced relatively modest phagocytic and nitric oxide responses of goldfish macrophages, rgIFN␥rel induced significantly higher phagocytosis, iNOSA and iNOSB gene expression and nitric oxide production compared with rgIFN␥. The rgIFN␥ and rgIFN␥rel induced different gene expression profiles in goldfish monocytes. These differences included significantly higher induction of TNF␣2, CXCL8, ceruloplasmin, and interferon regulatory factor (IRFs) expression after activation of monocytes with rgIFN␥rel. The rgIFN␥rel was more abundant in whole cell lysates compared with rgIFN␥. Both cytokines induced the phosphorylation of Stat1, while the nuclear localization of Stat1 was only observed following treatment of monocytes with rgIFN␥. Our findings suggest the presence of functional segregation of the induction of macrophage antimicrobial functions by type II interferons of bony fish.

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E 2 in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

“…IL-4/13A is highly expressed in the thymus, skin, and gills of salmon, and this has been associated with a role in early development of T cells, similar to that observed in mice, where IL-4 is a major Th2 response cytokine (33). Fish IFN-␥ has several functional properties in common with mammalian IFN-␥, including the ability to enhance respiratory burst activity, nitric oxide production, and phagocytosis of bacteria by macrophages (34)(35)(36). The role of these two cytokines during infection by S. parasitica needs to be further studied, but our data suggest they could be interesting markers for saprolegniosis resistance.…”

Prominent Amphibian (Xenopus laevis) Tadpole Type III Interferon Response to the Frog Virus 3 Ranavirus

“…IFN-␥, the only mammalian type II IFN (bony fish possess multiple type II IFNs [2]) has a plethora of immune and antiviral roles, whereas type I and III IFNs function predominantly as antiviral molecules. While type I IFNs affect a broad range of cell types, the type III IFNs (also known as IFN-or interleukin-28 and IL-29) act on a limited range of cell subsets (3,4).…”

Antiviral Activity of Salmonid Gamma Interferon against Infectious Pancreatic Necrosis Virus and Salmonid Alphavirus and Its Dependency on Type I Interferon

“…In contrast to the type I IFNs, fish and mammalian IFN-␥ are similar in exon/intron structure and display gene synteny. However, some fish species also possess a second IFN-␥ subtype named IFN gamma rel, which is quite different from the classical IFN-␥ (14). Rainbow trout and carp IFN-␥ have several functional properties in common with mammalian IFN-␥ including the ability to enhance respiratory burst activity, nitric oxide production, and phagocytosis of bacteria in macrophages (2,14,61).…”

“…However, some fish species also possess a second IFN-␥ subtype named IFN gamma rel, which is quite different from the classical IFN-␥ (14). Rainbow trout and carp IFN-␥ have several functional properties in common with mammalian IFN-␥ including the ability to enhance respiratory burst activity, nitric oxide production, and phagocytosis of bacteria in macrophages (2,14,61). Moreover, like mammalian IFN-␥, trout IFN-␥ induces the expression of IFN-␥ inducible protein 10 (IP-10), major histocompatibility complex class II ␤-chain, and STAT1 and signals through STAT1 (50,61).…”