TH-17 & enhanced RSV disease

ACOSTA, PL; WIMMENAUER, V; BRUM-ORNELAS C; SCALZO, PM; LAWRENCE A; HIJANO DR; NEWCOMB D; PRINCE G; PEEBLES RS; POLACK FP

Simposio; Vanderbilt International Symposium on Respiratory Virus Pathogenesis and Immunity; 2012

Vanderbilt University

Objective: Determine the role of Th17 in the enhanced disease (ERD) caused by respiratory syncytial virus (RSV) in toddlers immunized with an inactivated RSV vaccine (FIRSV). Study Design: Mice: 4-6 week old female BALB/c and C57BL/6 mice. Immunization: FIRSV 1x105 pfu, RSV 1x105 pfu, PBS (placebo) administered in footpad. Challenge: 60 days post-immunization, mice were challenged with RSV A2 106 pfu intranasally. Histopathology: Lung sections were stained with H&E and PAS. Cytokine responses and Th transcription factors were assayed in bronchoalveolar lavage fluids and regional lymph nodes by immunoasssay and real time RT-PCR. Lung sections from toddlers who died of ERD in 1967 were stained by immunohistochemistry. Results: Inactivated RSV vaccine enhances IL-17 production in regional lymph nodes after immunization compared to the response elicited by RSV or placebo. Th17 inmune response is enhanced in the lungs of mice with ERD and Th1 is suppressed ROR-γt (Th-17 master trancription factor) levels are increased in the lungs of mice with ERD. AHR and bronchipneumonia are decreased in mice treated with anti-neutrophils antibody AHR and bronchipneumonia are significantly decreased in mice treated with anti-IL-17 antibody. IL-17 positive cells are abundant in the lungs of toddlers killed by ERD in 1967. Exuberant neutrophilic infiltrate in the lungs of toddlers with RSV were found. Conclusions: Th-17 plays a key role in enhanced RSV disease.