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PLoS Pathog. 2019 Oct 11;15(10):e1008072. doi: 10.1371/journal.ppat.1008072. [Epub ahead of print] [h=1]Lung transcriptional unresponsiveness and loss of early influenza virus control in infected neonates is prevented by intranasal Lactobacillus rhamnosus GG.[/h]
Kumova OK[SUP]1[/SUP], Fike AJ[SUP]1[/SUP], Thayer JL[SUP]1[/SUP], Nguyen LT[SUP]2[/SUP], Mell JC[SUP]1[/SUP], Pascasio J[SUP]3[/SUP], Stairiker C[SUP]1,[/SUP][SUP]4[/SUP], Leon LG[SUP]4[/SUP], Katsikis PD[SUP]4[/SUP], Carey AJ[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h] 1 Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States of America. 2 Pediatrics, Drexel University College of Medicine, Philadelphia, PA, United States of America. 3 Pathology, Drexel University College of Medicine, Philadelphia, PA, United States of America. 4 Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.
[h=3]Abstract[/h] Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways. This is critical for protection, as neonatal mice intranasally pre-treated with IFNβ before influenza virus infection are also protected. Using transgenic mice, we demonstrate that the protective effect of LGG is mediated through a MyD88-dependent mechanism, specifically via TLR4. LGG can improve both early control of virus and transcriptional responsiveness and could serve as a simple and safe intervention to protect neonates.
PMID: 31603951 DOI: 10.1371/journal.ppat.1008072
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Kumova OK[SUP]1[/SUP], Fike AJ[SUP]1[/SUP], Thayer JL[SUP]1[/SUP], Nguyen LT[SUP]2[/SUP], Mell JC[SUP]1[/SUP], Pascasio J[SUP]3[/SUP], Stairiker C[SUP]1,[/SUP][SUP]4[/SUP], Leon LG[SUP]4[/SUP], Katsikis PD[SUP]4[/SUP], Carey AJ[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h] 1 Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States of America. 2 Pediatrics, Drexel University College of Medicine, Philadelphia, PA, United States of America. 3 Pathology, Drexel University College of Medicine, Philadelphia, PA, United States of America. 4 Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.
[h=3]Abstract[/h] Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways. This is critical for protection, as neonatal mice intranasally pre-treated with IFNβ before influenza virus infection are also protected. Using transgenic mice, we demonstrate that the protective effect of LGG is mediated through a MyD88-dependent mechanism, specifically via TLR4. LGG can improve both early control of virus and transcriptional responsiveness and could serve as a simple and safe intervention to protect neonates.
PMID: 31603951 DOI: 10.1371/journal.ppat.1008072
Free full text