A postbiotic supplementation in early life impacted Respiratory Syncytial Virus infection in mice

Abstract

Introduction

The Respiratory Syncytial Virus (RSV) causes severe bronchiolitis in children with 30% of them affected each year. Infection in neonates is characterised by a Th2 immune response and a low Th1 increasing the risk to develop asthma later. Oral probiotics supplementation reduced RSV infection by modulating the lung immune response [1]. However, no study describes nor the effect of postbiotics or inanimate bacteria in very early life.

Methods

Five-days-old BALBC mice were randomly divided into two groups, one receiving tyndallized Bifidobacterium breve LA708 (equivalent to 5 × 108 CFU before tyndallization) or the other PBS as negative control every day during 2 weeks. Luciferase recombinant RSV (205 × 103 pfu per animal) was intranasally inoculated at day 21 to half the mice in both groups. Infection was recorded in vivo by bioluminescence in lung and snout at 1.4 and 10 days post infection (dpi). Animals were necropsied and tissues and bronchoalveolar fluid (BALF) were collected for analysis of viral replication (bioluminescence activity) and lung inflammation (luminex assay and cytometry).

Results

All infected animals showed a mean radiance of around 1 × 104 in lungs and 1 × 105 in snouts at 1 and 4 dpi confirming the infection. B. breve LA708 showed no effect on infection at 1dpi in either the snouts or lungs. However, animals supplemented with B. breve LA708 exhibited lower infection in snouts at 4 dpi compared with animals supplemented with PBS. Similarly, although all mice were free of infection at 10 dpi in the LA708 group, a few mice still exhibited lung infection in the PBS one. An analysis of the immune response was then performed to decipher the effect of the strain. At 1 dpi, infected animals supplemented with B. breve LA708 showed a higher but non-significant number of polynuclear neutrophils and lymphocytes in BALF compared with infected control mice (P = 0.13) without affecting the total number of cells. Similarly, it seemed that IFN-b, TNF-a and IL-6 were increased in the lungs of animals supplemented with B. breve LA708 compared with infected control mice at 4 dpi. At 4 and 10 dpi, lungs of infected neonates supplemented with B. breve LA708 expressed an increased level of CD₄₅ + leucocytes compared to those supplemented with PBS with an enhance on the proportion of CD₈ + lymphocytes, NK cells and type 1 innate lymphoid cells (ILC1) among lymphocytes.

Conclusion

These data indicated that early supplementations with the postbiotic B. breve LA708 reduced infection in neonates, probably through a faster recruitment of innate immune cells and an activation of Th1 response in the lungs.