title: Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.
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.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: W
authors.initials: W
authors.lastname: Fonseca
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lucey
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Fujimura
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rasky
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: H-A
authors.initials: HA
authors.lastname: Ting
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: J
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Johnson
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Boushey
authors.affiliation: Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: E
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Department of Pediatrics, Augusta University, Augusta, Georgia, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Ownby
authors.affiliation: Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Levine
authors.affiliation: Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Bobbit
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Lynch
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D060833:Cellular Microenvironment; D065150:Cellular Reprogramming; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000378:metabolism; D056747:Immunomodulation; D000069999:Lactobacillus johnsonii / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004281:Docosahexaenoic Acids