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Expression of innate immunity genes and damage of primary human pancreatic islets by epidemic strains of Echovirus: implication for post-virus islet autoimmunity.

Sarmiento L, Frisk G, Anagandula M, Cabrera-Rode E, Roivainen M, Cilio CM - PLoS ONE (2013)

Bottom Line: The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects.Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4.These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.

View Article: PubMed Central - PubMed

Affiliation: Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmo, Sweden ; Department of Virology, "Pedro Kouri" Tropical Medicine Institute, Havana, Cuba.

ABSTRACT
Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS) were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively). In contrast, the expression of none of the innate immunity genes studied was altered in E4-infected islets. These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.

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Innate immunity gene expression in primary human islets cultured after three days of infection with clinical strains of E4, E16 and E30.Gene expression levels are presented as mRNA expression relative to expression of the housekeeping gene 18(2_dct). Data are presented as means ± SD and were based on observations from at least three donors. †P<0.05, between all groups (Islets infected with E4, E16, E30 and uninfected controls). *P<0.05, Islets infected with E16 and E30 were compared to E4-inoculated islets and the uninfected control.
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pone-0077850-g004: Innate immunity gene expression in primary human islets cultured after three days of infection with clinical strains of E4, E16 and E30.Gene expression levels are presented as mRNA expression relative to expression of the housekeeping gene 18(2_dct). Data are presented as means ± SD and were based on observations from at least three donors. †P<0.05, between all groups (Islets infected with E4, E16, E30 and uninfected controls). *P<0.05, Islets infected with E16 and E30 were compared to E4-inoculated islets and the uninfected control.

Mentions: Since recent studies reported that in vitro infection of human islets with HEV led to increased transcription of genes encoding IFN- b TLR 3, MDA5, RIG-I, RANTES and OAS [31], [32], we examine the expression of these innate immunity genes in isolated human pancreatic islets after infection with epidemic strains of echovirus. TLR3 and IFN-b mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively) compared to E4-inoculated islets and the uninfected control (Fig. 4). Infection with E16 and E30 also led to increased transcription of the innate immunity genes RIG-I, RANTES and OAS although this did not reach statistical significance (Fig. 4). In contrast, the gene-expression of RIG-I, TLR3, RANTES, OAS, and IFN-b, were not altered in E4-infected islets (Fig. 4).


Expression of innate immunity genes and damage of primary human pancreatic islets by epidemic strains of Echovirus: implication for post-virus islet autoimmunity.

Sarmiento L, Frisk G, Anagandula M, Cabrera-Rode E, Roivainen M, Cilio CM - PLoS ONE (2013)

Innate immunity gene expression in primary human islets cultured after three days of infection with clinical strains of E4, E16 and E30.Gene expression levels are presented as mRNA expression relative to expression of the housekeeping gene 18(2_dct). Data are presented as means ± SD and were based on observations from at least three donors. †P<0.05, between all groups (Islets infected with E4, E16, E30 and uninfected controls). *P<0.05, Islets infected with E16 and E30 were compared to E4-inoculated islets and the uninfected control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815302&req=5

pone-0077850-g004: Innate immunity gene expression in primary human islets cultured after three days of infection with clinical strains of E4, E16 and E30.Gene expression levels are presented as mRNA expression relative to expression of the housekeeping gene 18(2_dct). Data are presented as means ± SD and were based on observations from at least three donors. †P<0.05, between all groups (Islets infected with E4, E16, E30 and uninfected controls). *P<0.05, Islets infected with E16 and E30 were compared to E4-inoculated islets and the uninfected control.
Mentions: Since recent studies reported that in vitro infection of human islets with HEV led to increased transcription of genes encoding IFN- b TLR 3, MDA5, RIG-I, RANTES and OAS [31], [32], we examine the expression of these innate immunity genes in isolated human pancreatic islets after infection with epidemic strains of echovirus. TLR3 and IFN-b mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively) compared to E4-inoculated islets and the uninfected control (Fig. 4). Infection with E16 and E30 also led to increased transcription of the innate immunity genes RIG-I, RANTES and OAS although this did not reach statistical significance (Fig. 4). In contrast, the gene-expression of RIG-I, TLR3, RANTES, OAS, and IFN-b, were not altered in E4-infected islets (Fig. 4).

Bottom Line: The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects.Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4.These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.

View Article: PubMed Central - PubMed

Affiliation: Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmo, Sweden ; Department of Virology, "Pedro Kouri" Tropical Medicine Institute, Havana, Cuba.

ABSTRACT
Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS) were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively). In contrast, the expression of none of the innate immunity genes studied was altered in E4-infected islets. These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.

Show MeSH
Related in: MedlinePlus