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Polydnaviral ankyrin proteins aid parasitic wasp survival by coordinate and selective inhibition of hematopoietic and immune NF-kappa B signaling in insect hosts.

Gueguen G, Kalamarz ME, Ramroop J, Uribe J, Govind S - PLoS Pathog. (2013)

Bottom Line: These effects are blocked by the Vankyrin I²-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene.Additionally, their maternal expression weakens ventral embryonic patterning.We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature.

View Article: PubMed Central - PubMed

Affiliation: Biology Department, The City College of the City University of New York, New York, New York, United States of America.

ABSTRACT
Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyrins differentially impede Toll-NF-κB-dependent hematopoietic and immune signaling in a heterologous in vivo Drosophila, system. We first show that hematopoiesis and the cellular encapsulation response against parasitoid wasps are tightly-linked via NF-κB signaling. The niche, which neighbors the larval hematopoietic progenitors, responds to parasite infection. Drosophila NF-κB proteins are expressed in the niche, and non cell-autonomously influence fate choice in basal and parasite-activated hematopoiesis. These effects are blocked by the Vankyrin I²-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene. I²-vank-3 and P-vank-1 differentially obstruct cellular and humoral inflammation. Additionally, their maternal expression weakens ventral embryonic patterning. We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature.

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Effect of Vankyrins on D4-lacZ expression.A–A″. In uninfected Antp>GFP animals, D4-lacZ reporter is expressed strongly in the niche where it overlaps with Antp>GFP (A′–A″ – same image as in Fig. 2A–A″) and is sometimes found in a few cells in the anterior lobes. Expression of the D4-lacZ reporter is not changed in the niche when P1 is expressed (B–B″) but is clearly reduced by the expression of I3 (C–C″) compared to controls. D–D′. Same image as in Fig. 2B–B″. Infection strongly induces D4-lacZ expression in the niche and cells of the anterior lobes (compare D with A). E–E′. Expression of I3 in infected animals limits the induction of D4-lacZ in cells of the anterior lobes (compare intensity of β-Gal staining in cells of the anterior lobes in E′ versus D′ - t = 5.4, df = 27.1, p<0.001; N = 8 for Antp>GFP animals and N = 12 for Antp>GFP, I3 animals). F. Schematic linking NF-κB activity in the niche to choice of cell fate. Wild type control lymph glands (middle) with moderate NF-κB activity develop the correct proportion of crystal cells (CC), possess few if any constitutive lamellocytes (C, Lam), and abundant wasp-induced lamellocytes (WI Lam). Lack of NF-κB activity (left) shifts hematopoiesis in favor of crystal cells, while constitutive lamellocytes are absent and only a few wasp-induced lamellocytes are specified. High NF-κB (right; achieved either by infection or by genetic activation) shifts hematopoiesis in favor of lamellocytes and discourages crystal cell production.
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ppat-1003580-g005: Effect of Vankyrins on D4-lacZ expression.A–A″. In uninfected Antp>GFP animals, D4-lacZ reporter is expressed strongly in the niche where it overlaps with Antp>GFP (A′–A″ – same image as in Fig. 2A–A″) and is sometimes found in a few cells in the anterior lobes. Expression of the D4-lacZ reporter is not changed in the niche when P1 is expressed (B–B″) but is clearly reduced by the expression of I3 (C–C″) compared to controls. D–D′. Same image as in Fig. 2B–B″. Infection strongly induces D4-lacZ expression in the niche and cells of the anterior lobes (compare D with A). E–E′. Expression of I3 in infected animals limits the induction of D4-lacZ in cells of the anterior lobes (compare intensity of β-Gal staining in cells of the anterior lobes in E′ versus D′ - t = 5.4, df = 27.1, p<0.001; N = 8 for Antp>GFP animals and N = 12 for Antp>GFP, I3 animals). F. Schematic linking NF-κB activity in the niche to choice of cell fate. Wild type control lymph glands (middle) with moderate NF-κB activity develop the correct proportion of crystal cells (CC), possess few if any constitutive lamellocytes (C, Lam), and abundant wasp-induced lamellocytes (WI Lam). Lack of NF-κB activity (left) shifts hematopoiesis in favor of crystal cells, while constitutive lamellocytes are absent and only a few wasp-induced lamellocytes are specified. High NF-κB (right; achieved either by infection or by genetic activation) shifts hematopoiesis in favor of lamellocytes and discourages crystal cell production.

Mentions: Consistent with the interpretation that I3 may be able to block Dorsal/Dif function, we found, using the D4-lacZ reporter, that Antp>GFP, I3 (but not P1) reduces basal levels of β-galactosidase expression in the niche (Fig. 5A–C″). Moreover, wasp infection-induced boost in D4-lacZ expression in the lobes is also significantly inhibited by I3 with reduced β-galactosidase signal intensity (Fig. 5D–F).


Polydnaviral ankyrin proteins aid parasitic wasp survival by coordinate and selective inhibition of hematopoietic and immune NF-kappa B signaling in insect hosts.

Gueguen G, Kalamarz ME, Ramroop J, Uribe J, Govind S - PLoS Pathog. (2013)

Effect of Vankyrins on D4-lacZ expression.A–A″. In uninfected Antp>GFP animals, D4-lacZ reporter is expressed strongly in the niche where it overlaps with Antp>GFP (A′–A″ – same image as in Fig. 2A–A″) and is sometimes found in a few cells in the anterior lobes. Expression of the D4-lacZ reporter is not changed in the niche when P1 is expressed (B–B″) but is clearly reduced by the expression of I3 (C–C″) compared to controls. D–D′. Same image as in Fig. 2B–B″. Infection strongly induces D4-lacZ expression in the niche and cells of the anterior lobes (compare D with A). E–E′. Expression of I3 in infected animals limits the induction of D4-lacZ in cells of the anterior lobes (compare intensity of β-Gal staining in cells of the anterior lobes in E′ versus D′ - t = 5.4, df = 27.1, p<0.001; N = 8 for Antp>GFP animals and N = 12 for Antp>GFP, I3 animals). F. Schematic linking NF-κB activity in the niche to choice of cell fate. Wild type control lymph glands (middle) with moderate NF-κB activity develop the correct proportion of crystal cells (CC), possess few if any constitutive lamellocytes (C, Lam), and abundant wasp-induced lamellocytes (WI Lam). Lack of NF-κB activity (left) shifts hematopoiesis in favor of crystal cells, while constitutive lamellocytes are absent and only a few wasp-induced lamellocytes are specified. High NF-κB (right; achieved either by infection or by genetic activation) shifts hematopoiesis in favor of lamellocytes and discourages crystal cell production.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3757122&req=5

ppat-1003580-g005: Effect of Vankyrins on D4-lacZ expression.A–A″. In uninfected Antp>GFP animals, D4-lacZ reporter is expressed strongly in the niche where it overlaps with Antp>GFP (A′–A″ – same image as in Fig. 2A–A″) and is sometimes found in a few cells in the anterior lobes. Expression of the D4-lacZ reporter is not changed in the niche when P1 is expressed (B–B″) but is clearly reduced by the expression of I3 (C–C″) compared to controls. D–D′. Same image as in Fig. 2B–B″. Infection strongly induces D4-lacZ expression in the niche and cells of the anterior lobes (compare D with A). E–E′. Expression of I3 in infected animals limits the induction of D4-lacZ in cells of the anterior lobes (compare intensity of β-Gal staining in cells of the anterior lobes in E′ versus D′ - t = 5.4, df = 27.1, p<0.001; N = 8 for Antp>GFP animals and N = 12 for Antp>GFP, I3 animals). F. Schematic linking NF-κB activity in the niche to choice of cell fate. Wild type control lymph glands (middle) with moderate NF-κB activity develop the correct proportion of crystal cells (CC), possess few if any constitutive lamellocytes (C, Lam), and abundant wasp-induced lamellocytes (WI Lam). Lack of NF-κB activity (left) shifts hematopoiesis in favor of crystal cells, while constitutive lamellocytes are absent and only a few wasp-induced lamellocytes are specified. High NF-κB (right; achieved either by infection or by genetic activation) shifts hematopoiesis in favor of lamellocytes and discourages crystal cell production.
Mentions: Consistent with the interpretation that I3 may be able to block Dorsal/Dif function, we found, using the D4-lacZ reporter, that Antp>GFP, I3 (but not P1) reduces basal levels of β-galactosidase expression in the niche (Fig. 5A–C″). Moreover, wasp infection-induced boost in D4-lacZ expression in the lobes is also significantly inhibited by I3 with reduced β-galactosidase signal intensity (Fig. 5D–F).

Bottom Line: These effects are blocked by the Vankyrin I²-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene.Additionally, their maternal expression weakens ventral embryonic patterning.We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature.

View Article: PubMed Central - PubMed

Affiliation: Biology Department, The City College of the City University of New York, New York, New York, United States of America.

ABSTRACT
Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyrins differentially impede Toll-NF-κB-dependent hematopoietic and immune signaling in a heterologous in vivo Drosophila, system. We first show that hematopoiesis and the cellular encapsulation response against parasitoid wasps are tightly-linked via NF-κB signaling. The niche, which neighbors the larval hematopoietic progenitors, responds to parasite infection. Drosophila NF-κB proteins are expressed in the niche, and non cell-autonomously influence fate choice in basal and parasite-activated hematopoiesis. These effects are blocked by the Vankyrin I²-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene. I²-vank-3 and P-vank-1 differentially obstruct cellular and humoral inflammation. Additionally, their maternal expression weakens ventral embryonic patterning. We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature.

Show MeSH
Related in: MedlinePlus