title: Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.
abstract: We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24h after virus challenge. Survival in response to L. plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airways. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L. plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L. plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L. plantarum, as are mice devoid of type I interferon receptors. Taken together, L. plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms.
authors.affiliation: Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Percopo
authors.affiliation: Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Rice
authors.affiliation: Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Brenner
authors.affiliation: Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.affiliation: Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Luo
authors.affiliation: Genomics Unit, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
authors.forename: Kishore
authors.initials: K
authors.lastname: Kanakabandi
authors.affiliation: Genomics Unit, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.affiliation: Genomics Unit, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.affiliation: Department of Pediatrics, Upstate Medical University, State University of New York Upstate Medical University, Syracuse, NY, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.affiliation: Infectious Disease, Drug Discovery, Glaxo Smith Kline, Inc., Research Triangle Park, NC, USA.
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Keicher
authors.affiliation: Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: hrosenberg@niaid.nih.gov.
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D007155:Immunologic Factors / Q000008:administration & dosage*; D048191:Lactiplantibacillus plantarum / Q000276:immunology*; D052200:Limosilactobacillus reuteri / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus / Q000276:immunology*; D018186:Pneumovirus Infections / Q000473:pathology* / Q000628:therapy*; D019936:Probiotics / Q000008:administration & dosage*; D016019:Survival Analysis
chemical_list: D007155:Immunologic Factors
keywords: Cytokines; Inflammation; Pattern-recognition receptors; Pneumovirus