title: Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4.
abstract: Respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. Current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. Here, we demonstrate that a lysate derived from Gram-positive and Gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (RSV) and influenza virus in murine models of infection. Interestingly, despite the complex mixture of Toll-like receptor (TLR) agonists present in the bacterial lysate, the modulatory effects were mostly dependent on TLR4 signaling. Our results indicate that the use of simple formulations of TLR-agonists can significantly improve the immune response against critical pediatric respiratory pathogens.
authors.affiliation: a Fundación INFANT ; Buenos Aires , Argentina.
authors.forename: Silvina
authors.initials: S
authors.lastname: Coviello
authors.forename: Vera
authors.initials: V
authors.lastname: Wimmenauer
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Polack
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Irusta
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002457:Cell Extracts / Q000627:therapeutic use*; D002460:Cell Line; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000095983:Bacterial Lysates
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D002457:Cell Extracts; D053583:Interleukin-1beta; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates; C587672:IL1B protein, mouse; C508600:IL6 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse
keywords: RSV; adjuvants; bacterial; extracts; immunomodulators; influenza; lysates; respiratory; virus