Lactic acid Bacteria isolated from European badgers (Meles meles) reduce the viability and survival of Bacillus Calmette-Guerin (BCG) vaccine and influence the immune response to BCG in a human macrophage model

Abstract

BackgroundBovine tuberculosis (bTB) caused by Mycobacterium bovis is the most serious endemic disease affecting livestock in the UK. The European badger (Meles meles) is the most important wildlife reservoir of bTB transmission to cattle, making eradication particularly difficult. In this respect, oral vaccination with the attenuated M. bovis vaccine Bacillus Calmette-Guerin (BCG) has been suggested as a wide-scale intervention to reduce bTB infection in badgers. However, experimental studies show variable protection. Among the possibilities for this variation is that the resident gut bacteria may influence the success of oral vaccination in badgers; either through competitive exclusion and/or inhibition, or via effects on the host immune system. In order to explore this possibility, we have tested whether typical gut commensals such as Lactic Acid Bacteria (LAB) have the capacity to impact on the viability and survival rate of BCG and to modulate the immune response to BCG using an in vitro model.ResultsTwelve LAB isolated from badger faeces displayed inhibitory activity to BCG that was species-dependent. Weissella had a bacteriostatic effect, whereas isolates of enterococci, lactobacilli and pediococci had a more bactericidal activity. Furthermore, BCG-induced activation of the pro-inflammatory transcription factor NF-κB in human THP-1 macrophages was modulated by LAB in a strain-dependent manner. Most pediococci enhanced NF-κB activation but one strain had the opposite effect. Interestingly, isolates of enterococci, lactobacilli and weissella had different effects as immunomodulators of BCG-induced macrophage responses as some had no significant influence on NF-κB activation, but others increased it significantly.ConclusionsOur in vitro results show that LAB isolated from badgers exhibit significant inhibitory activity against BCG and influence the immune activation mediated by BCG in a human macrophage assay. These findings suggest that gut commensal bacteria could play a role in influencing the outcome of oral BCG vaccination. Inactivated cells of LAB, or LAB that are bacteriostatic but have a synergistic immunostimulatory effect with BCG, could be potential adjuvants to be used for oral vaccination in badgers. Further work is needed to take into account the complex nature of the gut microbiome, specific immunity of the badger and the in vivo context.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1210-z) contains supplementary material, which is available to authorized users.

Beneficial bacteria activate type-I interferon production via the cytosolic sensors STING and MAVS

“…This screen showed that LAB activate IFN-I production in human macrophages in a species-dependent manner as only LP and PP were able to induce a significant induction of luciferase in THP-1-IFIT1-GLuc macrophages. This species-dependent IFTI1 activation has also been observed with other strains of LP and PP that we have recently isolated from animals (38, 39). The central dogma is that LAB activate NF-κB via TLR2 (40), TLR9 (41) and Nod-like receptors (42).…”

Gut commensal bacteria show beneficial properties as wildlife probiotics

“…Furthermore, we have previously reported that lactobacilli and pediococci significantly reduce the survival rate of BCG in cocultures. 17 In this respect, it is likely that the production of bacteriocins by L. plantarum P5 and the pediococci strains B4 and I32 requires the presence of other bacterial cells, as previously reported. 80 In fact, the clusters involved in the biosynthesis of some of these bacteriocins contain genes associated with regulation.…”

“…Despite the fact that the phagocytes were not derived from badgers, our human model has proved to be informative at generating preliminary data that show the potential for badger LAB to cause immunomodulation, as previously described. 17 L. reuteri D4 and the P. acidilactici strains F7 and E24 were able to induce significantly the activation of NF-κB in THP-1 monocytes, while the IFN pathway was overstimulated in the same monocytes following exposure to P. pentosaceus B4, L. plantarum P5, and the enterococci isolates C34 and A7. When blood cells were challenged with all these isolates, we observed a significant phagocytic response, mainly from monocytes, implying the importance of bacterial phagocytosis for the activation of proinflammatory mediators via NF-κB and IFN.…”

“…14 Some studies have reported that LAB activate the production of type I interferon (IFN-I) in immune cells via endosomes through TLR2 and TLR3. 15,16 Recently, we have published that commensal LAB isolated from feces of badgers and wild boar have significant antimycobacterial activity, and influence the innate immunological interaction of macrophages with bacillus Calmette-Guerin (BCG), 17,18 suggesting a role for gut-resident bacteria in the host response to mycobacterial infection. Furthermore, our results raise the interesting possibility that LAB with significant antimycobacterial activity may be able to reduce the gut burden of M. bovis and other pathogenic microbes.…”

“…All displayed extracellular activity against Mycobacterium smegmatis at a low pH and reduced the viability and survival rate of M. bovis BCG when competing together in the same broth for 48 hours. 17 In the present study, further species analysis was carried out using the published Genbank genomes from E. faecalis, L. plantarum, L. reuterii, pediococci, and weissella with feature frequency profiling (FFP). 23 This technique allows both cross-species and cross-genus comparisons between genome sequences to confirm bacterial identification.…”