Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection.

Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-ß expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-ß, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-ß, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.

Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection.

Fucoidan, a sulfated polysaccharide isolated from an edible brown alga Undaria pinnatifida, was previously shown to be a potent inhibitor of the in vitro replication of herpes simplex virus type 1 (HSV-1). HSV-1 is a member of herpes viruses that cause infections ranging from trivial mucosal ulcers to life-threatening disorders in immunocompromised hosts. In the in vivo conditions, the replication of HSV-1 is controlled under the immunoresponse coordinated by both the innate and adaptive immune systems. In the present study, the effects of the fucoidan were examined on in vivo viral replication and the host's immune defense system. Oral administration of the fucoidan protected mice from infection with HSV-1 as judged from the survival rate and lesion scores. Phagocytic activity of macrophages and B cell blastogenesis in vitro were significantly stimulated by the fucoidan, while no significant change in the release of NO(2)(-) by macrophages was observed. In in vivo studies, oral administration of the fucoidan produced the augmentation of NK activity in HSV-1-infected mice immunosuppressed by 5-fluorouracil treatment. CTL activity in HSV-1-infected mice was also enhanced by oral administration of the fucoidan. The production of neutralizing antibodies in the mice inoculated with HSV-1 was significantly promoted during the oral administration of the fucoidan for 3 weeks. These results suggested that oral intake of the fucoidan might take the protective effects through direct inhibition of viral replication and stimulation of both innate and adaptive immune defense functions.

Suppression of Th2 immune responses by mekabu fucoidan from Undaria pinnatifida sporophylls.

BACKGROUND: We demonstrated that mekabu fucoidan obtained from Undaria pinnatifida (Up) sporophylls augments the type 1 T-helper (Th1) cell response in normal BALB/c mice. In this study, we examined the effects of the fucoidan of mekabu on the type 2 T-helper (Th2) response in bronchoalveolar lavage fluid (BALF) after ovalbumin (OVA) aerosol challenge. METHODS: Mekabu fucoidan (50 mg/kg) was injected intraperitoneally into BALB/c mice for 4 days, and then the mice were sensitized with 50 microg/mouse of OVA plus alum (1 mg/mouse) 1 and 8 days later. The mice were challenged with OVA delivered using a nebulizer 7, 8 and 9 days after the second challenge with OVA plus alum. After 24 h, we assessed T cell responses in BALF by measuring the amount of Th2 cytokines (IL-4, IL-5, IL-13) and gamma-interferon (IFN-gamma) produced by Th1 cells. RESULTS: The production of Th2 cytokines was suppressed (p < 0.05), and the amount of IFN-gamma was not increased in the mice treated with mekabu fucoidan. Anti-OVA immunoglobulin E (IgE) and IgE levels in serum determined after challenge with aerosolized OVA at the end of the experiment were lower (p < 0.05) in the treated than in the control mice. CONCLUSIONS: The pulmonary inflammation was relieved by mekabu fucoidan, which also downregulated Th2-dominated responses. These results indicate that mekabu fucoidan modulates Th2 responses and might be useful for treating allergic inflammation.