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Immunomodulatory and prophylactic effects of Bifidobacterium bifidum probiotic strain on influenza infection in mice

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Abstract

The limited efficacy of available influenza vaccines against rapidly emerging new viral strains stresses the need for the development of new antigen-independent prophylactic treatment for enhancing immunity against influenza infection. Recent studies suggest that probiotics possess immunomodulatory properties and can reduce the severity of respiratory infections. Here, we investigated the potential of prophylactic Bifidobacterium bifidum in improving anti-influenza immune responses in an experimental lethal mouse-adapted influenza A (H1N1) infection in a BALB/c mouse model. One week after viral challenge, splenocyte proliferation assay (MTT), IFN-gamma, IL-12, and IL-4 in spleen and IL-6 in the lung homogenates were conducted using ELISA assays. Sera samples were collected to measure IgG1 and IgG2a levels. Furthermore, the mice challenged with lethal influenza virus were assessed for survival rate. The findings demonstrated a strong induction of both humoral and cellular immunities, as well as decreased level of IL-6 production in the lung and an increase in survival rate in the mice receiving Bifidobacterium than those of the control group were observed. Taken together, the results indicate a robust potential for Bifidobacterium to modulate humoral and cellular immune responses and induce balanced Th1/Th2 immune responses against influenza infection.

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Abbreviations

MDCK:

Madin–Darby canine kidney

DMEM:

Eagle's minimal essential medium

CPE:

Cytopathic effect

p.i.:

Post-infection

TCID50:

The tissue culture infectious dose 50%

LD90:

The lethal dose

i.n.:

Intranasally

MOI:

Multiplicity of Infection

HEPES:

(4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid)

IgG:

Immunoglobulin G

PR8 virus:

Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)

HRP:

horseradish peroxidase

SI:

Stimulation Index

NKSF:

Natural killer cell stimulatory factor

TMB:

3,3,5,5-Tetramethylbenzidine

CTL:

Cytotoxic T lymphocyte

DC:

Dendritic cells

DMSO:

Dimethyl sulfoxide

ELISA:

Enzyme-linked immunosorbent assay

FBS:

Fetal bovine serum

IFN-γ:

Interferon γ

IL-4:

Interleukin 4

IL-12:

Interleukin 12

LPA:

Lymphocyte proliferation Assay

MTT:

3[4,5-Dimethylthiazol-2-ll]-2,5-diphenyltetrazolium bromide; thiazolyl-blue

OD:

Optical density

PHA:

Phytohemaglotinin

PBS:

Phosphate-buffered saline

RPMI:

1640 Roswell Park Memorial Institute (name of the medium)

Th:

T helper

SD:

Standard deviation

nm:

Nanometer

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Acknowledgements

The authors would like to acknowledge Pasteur Institute of Iran for the financial support. Also special thanks to Tak Gen Zist Company for providing probiotics.

Funding

This study was supported by Pasteur Institute of Iran (Grant No. 1370).

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Authors

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Correspondence to Amir Ghaemi.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The animal protocol used in this study was approved by the local animal ethics council of Pasteur Institute of Iran (Ethics Number: et-1370). All experimental procedures involving mice were performed in accordance with the national experimental guidelines.

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Mahooti, M., Abdolalipour, E., Salehzadeh, A. et al. Immunomodulatory and prophylactic effects of Bifidobacterium bifidum probiotic strain on influenza infection in mice. World J Microbiol Biotechnol 35, 91 (2019). https://doi.org/10.1007/s11274-019-2667-0

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  • DOI: https://doi.org/10.1007/s11274-019-2667-0

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