Lactobacillus johnsonii Supplementation Attenuates Respiratory Viral Infection via Metabolic Reprogramming and Immune Cell Modulation

2017-11
Mucosal Immunology 10(6)
- W. Fonseca
- Kaitlyn S. Lucey
- Sihyug Jang
- K. Fujimura
- A. Rasky
- Hung-An Ting
- J. Petersen
- C. Johnson
- H. Boushey
- E. Zoratti
- D. Ownby
- A. M. Levine
- Kevin R. Bobbit
- S. Lynch
- N. Lukacs

PubMed: 28295020
DOI: 10.1038/mi.2017.13

Study Design

Type: Clinical Trial
Population: Mice
Methods: Controlled experimental study

Rigorous Journal
Animal Study

Abstract

Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.

Research Insights

Lactobacillus johnsonii VPro 33→Altered CD4+ T-cell Cytokine Levels
RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had...modified CD4+ T-cell cytokines.
Effect
Beneficial
Effect size
Moderate
Lactobacillus johnsonii VPro 33→Altered Circulating Metabolic Profile
L. johnsonii supplementation...was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment.
Effect
Beneficial
Effect size
Moderate
Lactobacillus johnsonii VPro 33→Increased Regulatory T Cell Count
L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells...
Effect
Beneficial
Effect size
Moderate
Lactobacillus johnsonii VPro 33→Reduced Airway Pathological Responses
Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals.
Effect
Beneficial
Effect size
Large
Lactobacillus johnsonii VPro 33→Reduced Airway T Helper Type 2 Cytokines
L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells...
Effect
Beneficial
Effect size
Moderate
Lactobacillus johnsonii VPro 33→Reduced Dendritic Cell Function
L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells...
Effect
Beneficial
Effect size
Moderate