ToxSci Advance Access published online on June 15, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi225
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1 Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824; Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824; Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824
* To whom correspondence should be addressed. Based on the known capacity of deoxynivalenol (DON) to target gut lymphoid tissue and IgA production, it was hypothesized that this mycotoxin interferes with the immune response to enteric reovirus infection. When mice were orally gavaged first with 25 mg/kg DON bw and then with reovirus serotype 1, strain Lang (T1/L) 2 or 12 h later, viral titers in the GI tract were 10-fold higher than control mice after 5 d. Virus was almost completely cleared in both treatment and control groups from intestinal tissue after 10 d. Real-time PCR indicated that, in infected control mice, reovirus
Received March 24, 2005
Accepted June 9, 2005
Immunotoxiocology
Modulation of Murine Host Response to Enteric Reovirus Infection by the Trichothecene Deoxynivalenol
2 Department of Microbiology and Immunology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 26506
James Pestka, E-mail: pestka{at}msu.edu
Abstract 
2 core spike (L2 gene) RNA /g feces in infected mice that were pre-treated with DON was significantly higher at 1, 3 and 5 d than in infected mice only. In reovirus infected mice, DON at doses of 10 and 25 mg/kg bw but not 2 and 5 mg/kg increased fecal L2 RNA whereas DON doses as low as 2 mg/kg potentiated L2 RNA levels in Peyer's patches. Reovirus-specific IgA levels in feces of mice treated with DON were significantly elevated as were specific IgA responses in lamina propria and Peyer's patch fragment cultures. Similar effects were observed for serum IgA and IgG. DON suppressed IFN-
responses in PP to reovirus at 3 d and 5 d as compared to infected controls while IL-2 mRNA concentrations were unaffected. Although reovirus alone did not induce Th2 cytokine mRNAs in PP, DON exposure significantly elevated IL-4, IL-6, IL-10 mRNA expression at various times during the infection. ELISPOT revealed that mRNA expression data corresponded to suppression of IFN-- and enhancement of IL-4- producing cell responses in PP cultures from DON- treated mice. Taken together, these data suggest that DON transiently increased both severity of the reovirus infection and shedding in feces as well as elevated reovirus IgA responses. These effects corresponded to suppressed Th1 and enhanced Th2 cytokine expression.
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