Modulation of Murine Host Response to Enteric Reovirus Infection by the Trichothecene Deoxynivalenol

Abstract

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 bw DON, 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 days. Virus was almost completely cleared in both treatment and control groups from intestinal tissue after 10 days. Real-time PCR indicated that, in infected control mice, reovirus lambda2 core spike (L2 gene) RNA per g feces in infected mice that were pretreated with DON was significantly higher at 1, 3, and 5 days 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 bw increased fecal L2 RNA, whereas DON doses as low as 2 mg/kg potentiated L2 RNA levels in Peyer's patches (PP). Reovirus-specific IgA levels in feces of mice treated with DON were significantly elevated, as were specific IgA responses in lamina propria and PP fragment cultures. Similar effects were observed for serum IgA and IgG. DON suppressed IFN-gamma responses in PP to reovirus at 3 and 5 days 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, and IL-10 mRNA expression at various times during the infection. ELISPOT revealed that mRNA expression data corresponded to suppression of IFN-gamma- 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.

Zearalenone and deoxynivalenol mycotoxicosis in dairy cattle herds

“…When administered to monogastric animals, DON elicits a specific immune response which is manifested by increased Th2 activity and a drop in Th1 activity (Li et al 2005), as found in allergies (Luft et al 2008, Maresca andFantini 2010). A similar scenario is observed in rumen dysfunctions where DON acts as an antibacterial agent.…”

The effect of in vivo exposure to zearalenone on cytokine secretion by Th1 and Th2 lymphocytes in porcine Peyer’s patches after in vitro stimulation with LPS

“…Numerous studies have demonstrated that selected mycotoxins affect the Th1/Th2 balance. Li et al (2005) observed that doxynivalenol administered to mice activated Th2 populations and inhibited the Th1 immune response. Subclinical doses of patulin can alter the Th1/Th2 balance in favor of the Th2 immune response and promote allergic reactions and ulcerative colitis (Luft et al 2008).…”

In vitro effect of deoxynivalenol (DON) mycotoxin on porcine reproductive and respiratory syndrome virus replication

“…In mice, consumption of feed contaminated with T-2 toxin, another trichothecene, increased the susceptibility to Herpes simplex virus-1 (HSV-1) infection, by allowing virus proliferation, ultimately resulting in the death of mice naturally resistant to HSV-1 (Friend et al, 1983). Other studies in mice suggests that DON compromised resistance to enteric (Li et al, 2005) and respiratory (Li et al, 2007) reovirus infection.…”