Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections

Abstract

It has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. This study demonstrated that administration of heat-killed Enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. The influenza-mediated morbidity and lung inflammation in E. faecalis-treated mice decreased significantly compared with those of the control mice. Furthermore, we found that the protection is associated with production of monocyte chemoattractant protein-1 (MCP-1). The intratracheal injection of a recombinant mouse MCP-1 protein abrogated the antiviral effects elicited by pretreatment with E. faecalis. CC chemokine receptor 2 (CCR2) is a receptor for MCP-1, and the intraperitoneal administration of a CCR2 antagonist effectively inhibited viral pathogenicity. The reduced pathogenicity was also observed in CCR2-deficient mice. Finally, E. faecalis significantly attenuated neuropathogenicity induced by another RNA virus, enterovirus 71. This study demonstrates that killed probiotics can reduce viral disease severity and identify that the MCP-1 pathway might act as a key mediator in the improved antiviral immune response. Our findings suggest that MCP-1 and its related signaling pathway can serve as critical therapeutic targets for development of new antiviral strategies.

Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection

“…Our studies have showed that the immunomodulatory effect of some nasally administered immunobiotics persisted for at least 15 days (Villena et al, unpublished results). Other studies have also reported short-term protection after nasal treatment with different immunobiotic strains (43). Interestingly, Garcia-Crespo et al (52) found that adult mice primed nasally with L. plantarum NCIMB 8826 or Lactobacillus reuteri F275 were completely protected against lethal PVM infection and that protection persisted for at least 5 months after the initial priming.…”

“…Chen et al (43) also investigated the ability of orally administered Enterococcus faecalis KH2 to beneficially modulate the innate immune response to influenza infection. Authors observed that KH2 strain protected C57BL/6 mice against IFV as observed by the reduced mortality, weight loss, and lung viral titers.…”

“…Considering that monocyte migration mediated by MCP-1 has been linked to several respiratory inflammatory disorders including IFV infection, authors investigated the role of MCP-1/CCR2 pathway in the immunobiotic effect of E. faecalis KH2. The work reported that the protective activity of the KH2 strain was abrogated when recombinant MCP-1 was administered concomitantly (43). …”

Neuroprotective effect of Ruminococcus albus on oxidatively stressed SH-SY5Y cells and animals

“…It has been assumed that probiotic bacteria need to be alive to confer health benefits on the body when administered in an adequate amount; however, there have been concerns that live bacteria could cause unwanted side effects. To avoid these unwanted side effects, heat- or UV-inactivated bacteria have been assessed as a substitute, and their beneficial effects on the body were found to be similar to the benefits of live bacteria 6 , 18 , 19 . In addition, heat- or UV-inactivated bacteria possess several advantages such as safe, stable and easy handling compared with live bacteria.…”

Enhancing the natural killer cell activity and anti-influenza effect of heat-treated Lactobacillus plantarum nF1-fortified yogurt in mice

“…Various studies reported that heat-killed probiotics have a similar level of immunomodulatory abilities as live probiotics, despite a lack of viability. In case of Enterococcus faecalis and L. plantarum 06CC2, administration of heat-treated LAB on mice before influenza virus infection reduced morbidity and alleviated symptoms (Takeda et al, 2011;Chen et al, 2017b). Therefore, by using heattreated probiotics as an additive, it can be easier to increase immunomodulatory properties of yogurt with prolonged shelf life and easier storage properties.…”