Abstract
In this study, we investigate the potential for oral Lactobacilli (LB) to afford innate protection against nasopharyngeal coloniser Neisseria meningitidis serogroup B (NmB), which causes the bulk of UK meningococcal disease. Oral isolates of L. plantarum, L. salivarious, L. casei, L. rhamnosus, L. gasseri and gut probiotic L. rhamnosus GG were assessed for their ability to suppress nasopharyngeal epithelial inflammatory responses to pathogenic NmB. The specificity of attenuation was examined using TLR 2 ligand, Pam3Cys, and early response cytokine IL1β; and the mechanism of attenuation was explored using heat-killed organisms and conditioned medium. Pro-inflammatory IL-6 and TNFα cytokine secretion was quantified by ELISA and associated cell death was quantified by PI staining and LDH release. NmB adhesion, invasion and metabolism were determined using standard gentamicin protection with viable counts, and bioluminescence, respectively. L. plantarum and L. salivarious suppressed IL-6 and TNFα secretions from NmB-infected epithelial cells. LB did not need to be alive and could suppress using secretions, which were independent of TLR2 or IL1β receptor signalling. L. plantarum, in particular, reduced NmB-induced necrotic cell death of epithelial monolayers. Like L. salivarious, it significantly inhibited NmB adhesion but uniquely L. plantarum abolished NmB invasion. Using bioluminescence as a reporter of pathogen metabolism, L. plantarum and its secretions were found to inhibit NmB metabolism during cell invasion assays. We conclude that oral L. plantarum and its secretions could be used to help reduce the burden of meningococcal disease by removing the intracellular nasopharyngeal reservoir of NmB.
Highlights
The Gram-negative bacterium Neisseria meningitidis (Nm) is one of the main etiologic agents of bacterial meningitis and septicaemia [1]
Oral L. plantarum and L. salivarius were able to attenuate Neisseria meningitidis serogroup B (NmB) induced IL-6 and TNF-α during co-culture by approximately 50% - 70% compared with NmB alone
Conditioned media (CM) containing secretions from live L. plantarum and L. salivarius but not L. casei were found to strongly attenuate the IL-6 response induced by NmB by 42% (P < 0.001) - 62% (P < 0.05), which we suggest contributes to the strong ability of these strains to attenuate in live co-cultures
Summary
The Gram-negative bacterium Neisseria meningitidis (Nm) is one of the main etiologic agents of bacterial meningitis and septicaemia [1]. It is associated with a significant mortality and has a case fatality rate of 10% [2] reaching up to 55% in patients with fulminant septicae-. Despite significant progress made in the management of patients and the availability of vaccines against serogroups A, C, Y and W135, serogroup B (NmB) disease remains a major public health problem in the UK, Europe and the Australias, accounting for 85% 90% of meningococcal disease cases in the UK [4].
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