Childrens Foundation Research Institute

Memphis, TN, United States

Childrens Foundation Research Institute

Memphis, TN, United States

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Bagga B.,University of Tennessee Health Science Center | Bagga B.,Le Bonheur Childrens Hospital | Bagga B.,Childrens Foundation Research Institute | Cehelsky J.E.,Alnylam Pharmaceuticals | And 11 more authors.
Journal of Infectious Diseases | Year: 2015

We studied preexisting respiratory syncytial virus (RSV)- specific serum and nasal antibodies and their correlation with infectivity, viral dynamics, and disease severity in a human experimental infection model. Higher preinoculation serum neutralizing antibody titers and nasal immunoglobulin (Ig) A predicted lower infectivity and lower measures of viral replication. However, once individuals were infected, no significant protective effect of preexisting antibodies was seen. Lack of correlation between serum and mucosal antibodies was observed, implying that they are independent co-correlates of protection against RSV infection. We suggest that protection from RSV infection is a function of a complex interplay between mucosal and serum humoral immune responses. © The Author 2015. Published by Oxford University Press on behalf of the Infectious.


Oshansky C.M.,St Jude Childrens Research Hospital | Gartland A.J.,Fred Hutchinson Cancer Research Center | Wong S.-S.,St Jude Childrens Research Hospital | Jeevan T.,St Jude Childrens Research Hospital | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2014

Rationale: Children are an at-risk population for developing complications following influenza infection, but immunologic correlates of disease severity are not understood. We hypothesized that innate cellular immune responses at the site of infection would correlate with disease outcome. Objectives: To test the immunologic basis of severe illness during natural influenza virus infection of children and adults at the site of infection. Methods: Anobservational cohort study with longitudinal sampling of peripheral and mucosal sites in 84 naturally influenza-infected individuals, including infants. Cellular responses, viral loads, and cytokines were quantified from nasal lavages and blood, and correlated to clinical severity. Measurements and Main Results: We show for the first time that although viral loads in children and adults were similar, innate responses in the airways were stronger in children and varied considerably between plasma and site of infection. Adjusting for age and viral load, an innate immune profile characterized by increased nasal lavage monocyte chemotactic protein-3, IFN-a2, and plasma IL-10 levels at enrollment predicted progression to severe disease. Increased plasma IL-10, monocyte chemotactic protein-3, and IL-6 levels predicted hospitalization. This inflammatory cytokine production correlated significantly with monocyte localization from the blood to the site of infection, with conventional monocytes positively correlating with inflammation. Increased frequencies of CD14lo monocytes were in the airways of participants with lower inflammatory cytokine levels. Conclusions: An innate profile was identified that correlated with disease progression independent of viral dynamics and age. The airways and blood displayed dramatically different immune profiles emphasizing the importance of cellular migration and localized immune phenotypes. © 2014 by the American Thoracic Society.

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