Brief dexamethasone treatment during acute infection prevents virus-induced autoimmune diabetes

Londono, Pilar; Komura, Akiko; Hara, Naoko; Zipris, Danny

doi:10.1016/j.clim.2010.01.007

Cited by 28 publications

(40 citation statements)

References 45 publications

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“…These observations are consistent with the hypothesis that the innate immune system plays a key role in the mechanism leading to T1D in humans and in animal models (25,26,28,29,52). In the LEW1.WR1 rat, infection with KRV leads to a robust innate proinflammatory response in the spleen and pancreatic lymph nodes, and a reduction in the inflammation suppresses the development of virus-induced T1D (26,29,46). It remains to be seen whether and how pancreatic islets are involved in the mechanism of disease prevention.…”

Section: Discussionsupporting

confidence: 89%

“…We have previously demonstrated that infection with KRV induces a robust activation of the innate immune system in the pancreatic lymph nodes and pancreatic islets on day 5 postinfection (26,29,46). We hypothesized that the KRV-induced inflammation is likely to play a key role in the development of T1D (25), as reflected by alterations in the expression of proinflammatory mediators in the pancreatic lymph nodes and Peyer's patches.…”

Section: Antibiotic Therapy Reduces Krv-induced Inflammation In the Pmentioning

confidence: 99%

“…We have previously shown that the infection of LEW1.WR1 rats with KRV alters the cellular composition of the pancreatic lymph nodes shortly postinfection (46). We tested the possibility that virus-induced T1D and Sulfatrim-induced disease prevention are associated with altered lymphocyte cell numbers in the pancreatic lymph nodes and Peyer's patches.…”

Section: Sulfatrim Alters the B Lymphocyte Compartment In The Pancreamentioning

confidence: 99%

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Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy

Hara

Alkanani

et al. 2012

The Journal of Immunology

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111

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Microbes were hypothesized to play a key role in the progression of type 1 diabetes (T1D). We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced T1D to test the hypothesis that the intestinal microbiota is involved in the mechanism leading to islet destruction. Treating LEW1.WR1 rats with KRV and a combination of trimethoprim and sulfamethoxazole (Sulfatrim) beginning on the day of infection protected the rats from insulitis and T1D. Pyrosequencing of bacterial 16S rRNA and quantitative RT-PCR indicated that KRV infection resulted in a transient increase in the abundance of Bifidobacterium spp. and Clostridium spp. in fecal samples from day 5- but not day 12-infected versus uninfected animals. Similar alterations in the gut microbiome were observed in the jejunum of infected animals on day 5. Treatment with Sulfatrim restored the level of intestinal Bifidobacterium spp. and Clostridium spp. We also observed that virus infection induced the expression of KRV transcripts and the rapid upregulation of innate immune responses in Peyer’s patches and pancreatic lymph nodes. However, antibiotic therapy reduced the virus-induced inflammation as reflected by the presence of lower amounts of proinflammatory molecules in both the Peyer’s patches and pancreatic lymph nodes. Finally, Sulfatrim treatment reduced the number of B cells in Peyer’s patches and downmodulated adaptive immune responses to KRV, but did not interfere with antiviral Ab responses or viral clearance from the spleen, pancreatic lymph nodes, and serum. The data suggest that gut microbiota may be involved in promoting virus-induced T1D in the LEW1.WR1 rat model.

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Section: Discussionsupporting

confidence: 89%

Section: Antibiotic Therapy Reduces Krv-induced Inflammation In the Pmentioning

confidence: 99%

Section: Sulfatrim Alters the B Lymphocyte Compartment In The Pancreamentioning

confidence: 99%

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Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy

Hara

Alkanani

et al. 2012

The Journal of Immunology

Self Cite

111

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show abstract

“…A similar treatment blocked a more aggressive form of diabetes induced by Poly(I:C) pretreatment plus virus infection. Strikingly, a treatment with Poly(I:C), KRV, and a single dose of dexamethasone on the day of infection was sufficient to prevent disease in ∼50% of the animals [19]. Dexamethasone blocked disease without compromising the ability of the immune system to eliminate the virus from the host.…”

Section: Anti-inflammatory Therapy Prevents Virus-induced Diabetesmentioning

confidence: 98%

“…Dexamethasone is a potent anti-inflammatory and immunosuppressive glucocorticoid widely used in the clinic for treating many inflammatory disorders, such as allergic diseases, and autoimmunity [38]. It was evident that a brief treatment with low-dose dexamethasone on five consecutive days beginning on the day of infection completely blocked diabetes development [19]. A similar treatment blocked a more aggressive form of diabetes induced by Poly(I:C) pretreatment plus virus infection.…”

Section: Anti-inflammatory Therapy Prevents Virus-induced Diabetesmentioning

confidence: 99%