A role for Th-17 lymphocytes in Enhanced RSV Disease

ACOSTA, PL; SCALZO PM; WIMMENAUER, V; BRUM-ORNELAS C; PRINCE G; PEEBLES RS; POLACK FP

Rotterdam, Netherlands

Simposio; 7th International Respiratory Syncytial Virus Symposium; 2010

GCO Associations BV

A ROLE FOR TH-17 LYMPHOCYTES IN ENHANCED RSV DISEASE Objetive: Determine the role of the immune system response Th-17 and pathogenic mechanisms generated by respiratory syncytial virus inactivated vaccine (FIRSV) against respiratory syncytial virus (RSV) in a mouse model. Study Desing: FIRSV 1x 105 pfu, RSV 1x 105 pfu or PBS (placebo) vaccines performed footpad. We Challenge mice 60 days later with RSV A2 1x106 pfu intranasally. Histopathology, cell differentials, cytokine responses, transcription factors. We stained lung sections hystopathology of toddlers who died of ERD in 1967. Results: •FIRSV enhances IL-17 production in regional lymph nodes after immunization. •Th-1 response is suppressed, and Th-2 and Th-17 response is enhanced. •ROR-ãt (Th-17 master trancription factor) is greatly increased. •Airways hyperreactivity is drecreased when IL-17 is blocked. Conclusions: •FIRSV elicits a strong IL-17 response in regional lymph nodes after immunization. •IL-17 production is enhanced in the lungs of BALB/c and B6 mice with ERD, compared to mice with primary RSV infection or protected from challenge by a previous inoculation of wtRSV. •IL-17 production appears to associate with increased AHR in B6 mice with ERD. •Lung sections of toddlers who died of ERD in 1967 have a widespread neutrophilic infiltrate with abundant IL-17 producing cells. •The role Th17 and Treg cells in ERD requires further investigation.