Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection

Antiviral Res. 2015 Sep;121:109-19. doi: 10.1016/j.antiviral.2015.07.001. Epub 2015 Jul 2.

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.

Keywords: Cytokines; Inflammation; Pattern-recognition receptors; Pneumovirus.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Immunologic Factors / administration & dosage*
  • Lactobacillus plantarum / immunology*
  • Lactobacillus reuteri / immunology*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Murine pneumonia virus / immunology*
  • Pneumovirus Infections / pathology*
  • Pneumovirus Infections / therapy*
  • Probiotics / administration & dosage*
  • Survival Analysis

Substances

  • Immunologic Factors