Streptococcus Pneumoniae Infection in Respiratory Syncytial Virus Infected Neonatal Lambs

Abstract

Respiratory syncytial virus (RSV) is the main cause of viral bronchiolitis resulting in hospitalization and a frequent cause of secondary respiratory bacterial infection especially by Streptococcus pneumoniae (Sp) in infants. While murine studies have demonstrated enhanced morbidity during a viral/bacterial co‐infection, human meta‐studies have been mixed. Moreover, less is known about pathogenesis of Sp serotype 22 and especially the co‐pathologies between RSV and Sp dual infections.Here, we sought to examine mechanisms contributing to co‐pathogen‐induced morbidity using a large neonatal lamb animal model naturally permissive to infection by both pathogens.Colostrum deprived lambs (aged 3–5 days) were randomly divided into four groups. Two of the groups were nebulized with RSV M37 (1.27 × 107 IFFU/mL), and the other two group nebulized with cell–conditioned mock media. At day 3 post‐infection, one RSV group (RSV/Sp) and one mock‐nebulized group (Sp only) were infected with (2×106 cfu of Sp) intratracheally. At day 6 post‐infection all lambs were humanely euthanized and bacterial/viral pathogeneses were assessed by culture, focus forming unit, qPCR, IHC, and histopathology.Lambs dually infected with RSV and Sp had higher RSV titers by qPCR but lower Sp than the other comparable groups. Additionally, lung lesions were more intense in the RSV/Sp group as characterized by increased interalveolar wall thickness with neutrophils and lymphocyte infiltration.Despite lower Sp in lungs, lambs co‐infected with RSV exhibited greater morbidity and tissue histopathology. Thus, enhanced disease severity may be due more to elevated immunopathogenesis than elevated bacterial pathogenesisSupport or Funding Informationfunded by Merck & Company Inc.55211 Verhoeven, 11/01/16–10/31/18This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.