Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation
Fonseca W, Lucey K, Jang S, Fujimura KE, Rasky A, Ting HA, Petersen J, Johnson CC, Boushey HA, Zoratti E, Ownby DR, Levine AM, Bobbit KR, Lynch SV, and Lukacs NW. Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation. Mucosal Immunol 2017; 10(6):1569-1580.
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.
Medical Subject Headings
Animals; Bone Marrow Cells; Cell Line; Cellular Microenvironment; Cellular Reprogramming; Cytokines; Dendritic Cells; Dietary Supplements; Docosahexaenoic Acids; Immunomodulation; Lactobacillus johnsonii; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; T-Lymphocytes, Regulatory; Th2 Cells