Inhibition of Virus-Induced Diabetes Mellitus by Interferon is Influenced by the Host Strain

Giron, David; Cohen, Stuart J.; Lyons, Shayesteh P.; Wharton, Charles H.; Cerutis, D. Roselyn

doi:10.3181/00379727-173-41651

Cited by 20 publications

(14 citation statements)

References 6 publications

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“…Mice were infected by intraperitoneal (i.p.) injection with 800 plaque‐forming units of EMCV‐D 44 . Glucose tolerance tests (GTT) were performed by i.p.…”

Section: Methodsmentioning

confidence: 99%

Innate immune response to encephalomyocarditis virus infection mediated by CD1d

et al. 2003

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SUMMARYCD1d-reactive natural killer T (NKT) cells can rapidly produce T helper type 1 (Th1) and/or Th2 cytokines, can activate antigen-presenting cell (APC) interleukin-12 (IL-12) production, and are implicated in the regulation of adaptive immune responses. The role of the CD1d system was assessed during infection with encephalomyocarditis virus (EMCV-D), a picornavirus that causes acute diabetes, paralysis and myocarditis. EMCV-D resistance depends on IL-12-mediated interferon-g (IFN-g) production. CD1d-de®cient mice, which also lack CD1d-reactive NKT cells, were substantially more sensitive to infection with EMCV-D. Infected CD1d knockout mice had decreased IL-12 levels in vitro and in vivo, and indeed were protected by treatment with exogenous IL-12. IFN-g production in CD1d knockout mice was decreased compared with that in wild-type (WT) mice in response to EMCV-D in vitro, although differences were not detected in vivo. Treatment with anti-asialo-GM1 antibody, to deplete NK cells, caused a marked increase in susceptibility of WT mice to EMCV-D infection, whereas CD1d knockout mice were little affected, suggesting that NK-cell-mediated protection is CD1d-dependent. Therefore, these data indicate that CD1d is essential for optimal responses to acute picornaviral infection. We propose that CD1d-reactive T cells respond to early immune signals and function in the innate immune response to a physiological viral infection by rapidly augmenting APC IL-12 production and activating NK cells.

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“…Mice were infected by intraperitoneal (i.p.) injection with 800 plaque‐forming units of EMCV‐D 44 . Glucose tolerance tests (GTT) were performed by i.p.…”

Section: Methodsmentioning

confidence: 99%

Innate immune response to encephalomyocarditis virus infection mediated by CD1d

et al. 2003

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“…CD1d1 molecules and NKT cells have been shown to be important in other virus infections as well, particularly with regard to virus-mediated pathology. For example, an encephalomyocarditis virus (EMCV) infection of normal mice results in diabetes and CNS effects in a subset of those mice infected (57)(58)(59)(60)(61). When CD1KO mice are infected with EMCV, a substantially greater percentage of mice develop both diabetes and paralysis (62).…”

Section: Figurementioning

confidence: 99%

CD1d1-Dependent Control of the Magnitude of an Acute Antiviral Immune Response

Roberts

Lin

Spence

et al. 2004

The Journal of Immunology

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CD1d1-restricted NK T (NKT) cells rapidly secrete both Th1 and Th2 cytokines upon activation and are therefore thought to play a regulatory role during an immune response. In this study we examined the role of CD1d1 molecules and NKT cells in regulating virus-induced cytokine production. CD1d1-deficient (CD1KO) mice, which lack NKT cells, were infected with lymphocytic choriomeningitis virus, and spontaneous cytokine release from splenocytes was measured. We found that CD1KO mice produce significantly higher amounts of IL-2, IL-4, and IFN-γ compared with wild-type controls postinfection. Depletion studies of individual lymphocyte subpopulations suggested that CD4+ T cells are required; however, isolation of specific lymphocyte populations indicated that CD4+ T cells alone are not sufficient for the increase in cytokine production in CD1KO mice. Splenocytes from lymphocytic choriomeningitis virus-infected CD1KO mice continued to produce enhanced cytokine levels long after viral clearance and cleared viral RNA faster than wild-type mice. There was no difference in the number of splenocytes between uninfected wild-type and CD1KO mice, whereas the latter knockout mice had an increased number of splenocytes after infection. Collectively, these data provide clear evidence that the expression of CD1d1 molecules controls the magnitude of the cell-mediated immune response to an acute viral infection.

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“…Furthermore, the D variant was in a linear phase of attachment over the range of MOI tested, whereas that of EMC-B virus was nearly saturated at a low MOI. this hypothesis (6). 3).…”

Section: Attachment Of Encephalomyocarditis (Emc)-d and Emc-b Virusmentioning

confidence: 84%

“…Be-cause it has been shown that EMC-B virus is a good inducer of interferon (IFN), whereas EMC-D virus induces little or no IFN (1), it has been suggested that IFN produced during the early stages of EMC-B virus infection plays a role in protecting the p-cells from viral destruction. Indeed, we have evidence and have reported that exogenously administered IFN-a and -3 or poly I:C protects SWR/J but not ICR Swiss mice against the diabetogenic effects of EMC-D virus (6). For example, Gadzik et al (4) reported that a single injection of the IFN-inducer polyinosinic-polycytidylic acid (poly I:C) protects SWR/J mice against the diabetogenic effects of EMC-M virus, an EMC virus from which both the D and B variants were isolated (1).…”

mentioning

confidence: 86%

Differing Attachment of Diabetogenic and Nondiabetogenic Variants of Encephalomyocarditis Virus to β-Cells

Kaptur

Thomas²,

Giron³

1989

Diabetes

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The D variant of encephalomyocarditis (EMC-D) virus does not induce the production of interferon (IFN) and produces an insulin-dependent diabetes mellitus (IDDM)-like syndrome in certain mouse strains. In contrast, the B variant (EMC-B) virus, which is serologically identical to EMC-D virus, is a good inducer of IFN and is nondiabetogenic. It has been postulated that IFN may play a major role in determining the ability of these two viruses to infect pancreatic beta-cells. However, recent studies have shown that ICR Swiss and BALB/cByJ male mice are not protected by IFN against EMC-D virus-induced IDDM. Furthermore, treatment of these two strains of mice with anti-IFN gamma-globulin before infection with EMC-B virus does not result in diabetes. These observations suggest that mechanisms other than the IFN system are involved in determining the ability of the viruses to infect and destroy beta-cells. Studies were initiated to identify other mechanisms of action. In this communication, we show that up to six times more EMC-D than EMC-B virus attaches to primary beta-cells extracted from male ICR Swiss mice. This difference in ability to attach to beta-cells may account for the difference in the diabetic potential of this mouse strain.

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Inhibition of Virus-Induced Diabetes Mellitus by Interferon is Influenced by the Host Strain

Cited by 20 publications

References 6 publications

Innate immune response to encephalomyocarditis virus infection mediated by CD1d

Innate immune response to encephalomyocarditis virus infection mediated by CD1d

CD1d1-Dependent Control of the Magnitude of an Acute Antiviral Immune Response

Differing Attachment of Diabetogenic and Nondiabetogenic Variants of Encephalomyocarditis Virus to β-Cells

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