Abstract
When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp. lactis JCM5805 (JCM5805) is a strain of lactic acid bacteria (LAB) that activates murine and human pDCs to express type I and type III interferons (IFNs). JCM5805 has also been shown to activate pDCs via a Toll-like receptor 9 (TLR9) dependent pathway. In this study, we investigated the anti-viral effects of oral administration of JCM5805 using a mouse model of murine parainfluenza virus (mPIV1) infection. JCM5805-fed mice showed a drastic improvement in survival rate, prevention of weight loss, and reduction in lung histopathology scores compared to control mice. We further examined the mechanism of anti-viral effects elicited by JCM5805 administration using naive mice. Microscopic observations showed that JCM5805 was incorporated into CD11c+ immune cells in Peyer’s patches (PP) and PP pDCs were significantly activated and the expression levels of IFNs were significantly increased. Interestingly, nevertheless resident pDCs at lung were not activated and expressions levels of IFNs at whole lung tissue were not influenced, the expressions of anti-viral factors induced by IFNs, such as Isg15, Oasl2, and Viperin, at lung were up-regulated in JCM5805-fed mice compared to control mice. Therefore expressed IFNs from intestine might be delivered to lung and IFN stimulated genes might be induced. Furthermore, elevated expressions of type I IFNs from lung lymphocytes were observed in response to mPIV1 ex vivo stimulation in JCM5805-fed mice compared to control. This might be due to increased ratio of pDCs located in lung were significantly increased in JCM5805 group. Taken together, a specific LAB strain might be able to affect anti-viral immunological profile in lung via activation of intestinal pDC leading to enhanced anti-viral phenotype in vivo.
Highlights
Probiotics are live microorganisms in intestinal flora or starter cultures for dairy products that have been reported to have beneficial effects on human health
We found that oral administration of JCM5805 protected mice against Murine parainfluenza virus type 1 (mPIV1) infection by activating an immune response in lung tissue by stimulating plasmacytoid dendritic cells (pDCs) localized in the intestine
A number of studies have reported that Lactic acid bacteria (LAB) have some beneficial anti-viral effects against influenza virus in mice [3,4,5,6,7,8], by oral administration of L. plantarum 06CC2 (10 mg/day/ mouse) or L. acidophilus L-92 (10 mg/day/mouse), or intranasal administration of L. pentosus S-PT84 (20 or 200 μg/day/mouse) or L. casei shirota (20 or 200 μg/day/mouse)
Summary
Probiotics are live microorganisms in intestinal flora or starter cultures for dairy products that have been reported to have beneficial effects on human health. Lactic acid bacteria (LAB) had been reported to produce potent and diverse immunomodulatory effects. The protective effect of LAB against viral infection is of particular interest. Oral administration of Bifidobacterium breve YIT4064 has been shown to be effective against rotavirus-induced diarrhea and influenza virus infection [1,2]. Lactobacillus pentosus S-PT84, L. plantarum 06CC2, L. acidophilus L-92, Enterococcus faecalis FK-23 and L. casei shirota have been reported to protect mice from influenza virus infection [3,4,5,6,7,8]. Little is known about the mechanism of the effect of LAB on viral infection
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