Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice

Abstract

Background: The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection.

Methods: We intranasally infected BALB/c mice with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice. Seven days later, a secondary bacterial infection was induced by intranasal administration of bioluminescent N. meningitidis. During the experiment, mice orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect of L. paracasei administration on secondary bacterial infection by N. meningitidis was evaluated.

Results: Oral consumption of L. paracasei CNCM I-1518 reduced the weight loss of infected mice and lowered the bioluminescent signal of infecting meningococci. This improvement was associated with higher recruitment of inflammatory myeloid cells, such as interstitial monocytes and dendritic cells, to the lungs.

Conclusions: Our data highlight the role of the gut-lung axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and secondary bacterial infection, which should be further studied and validated in clinical trials.

Keywords: Inflammation; Influenzae; Meningococci; Mice; Neisseria meningitidis; Probiotics; Secondary infection.

Fig. 1

Effects of L. paracasei consumption on the health status of influenza/N. meningitidis-infected mice. a Schematic representation of the experimental design. b Body-weight loss. c Mortality. d Scores for the appearance of the mice after influenza infection as follows: 3; smooth coat, 2; patches of fur showing piloerection, 1; most of the fur showing piloerection, and 0; mouse appears “puffy”. Results are expressed as the mean ± SEM for each group (n = 50). (*p < 0.05, **P < 0.01, ***P < 0.001)

Fig. 2

Dissemination of N. meningitidis in BALB/c-flu infected mice. Sequential IAV (250 PFU per mouse) and meningococcal infection (10⁷ CFU per mouse) were performed by the intranasal route. Bacterial infection was analysed by bioluminescence at the indicated times. Images depict photographs overlaid with colour representations of luminescence intensity, measured in total photons/s and indicated on the scales, in which red is the most intense and blue the least intense. a Ventral views of nine PBS-fed and 10 L. paracasei-fed mice. A non-infected mouse was added as a control. b. The luminescence was quantified and expressed as the means ± SEM for each category at the indicated times by defining specific representative regions of interest encompassing the entire animal

Fig. 3

Effects of L. paracasei consumption on cytokine profiles relative to those of the control (PBS) group after 48 h of secondary meningococcal infection. Results are expressed as the mean ± SEM for each group (n = 20). Cytokines for which the differences between the two groups were significant are indicated by a star

Fig. 4

Effect of L. paracasei consumption on immune-cell recruitment to the lungs relative to that of the control (PBS) group after 48 h of secondary meningococcal infection. Results are expressed as the mean ± SEM for each group (n = 16). Cells for which the differences between the two groups were significant are indicated by a star