Differential impact of respiratory syncytial virus and parainfluenza virus on the frequency of acute otitis media is explained by lower adaptive and innate immune responses in otitis-prone children.
BACKGROUND
Acute otitis media (AOM) is a leading cause of bacterial pediatric infections associated with viral upper respiratory infections (URIs). We examined the differential impact of respiratory syncytial virus (RSV) and parainfluenza virus URIs on the frequency of AOM caused by Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in stringently defined otitis-prone (sOP) and non-otitis-prone (NOP) children as a potential mechanism to explain increased susceptibility to AOM.


METHODS
Peripheral blood and nasal washes were obtained from sOP and NOP children (n = 309). Colonization events and antiviral responses consisting of total specific immunoglobulin G (IgG) responses, neutralizing antibody responses, and T-cell responses were determined. Isolated neutrophils were infected with varying multiplicities of infection of both viruses, and opsonophagocytosis potential was measured.


RESULTS
A significant increase was found in frequency of AOM events caused by Spn and NTHi, with a concurrent RSV infection in sOP children. These results correlated with diminished total RSV-specific IgG, higher viral nasal burdens, and lower IgG neutralizing capacity. The sOP children had diminished T-cell responses to RSV that correlated with lower Toll-like receptor 3/7 transcript and decreased expression of HLA-DR on antigen-presenting cells. RSV interfered with the Spn phagocytic capacity of neutrophils in a dose-dependent manner. Parainfluenza virus infections did not differentially affect AOM events in sOP and NOP children.


CONCLUSIONS
Lower innate and adaptive immune responses to RSV in sOP children may slow the kinetics of viral clearance from the nasopharynx and allow for viral interference with antibacterial immune responses, thus contributing to increased frequency of AOMs.
Rochester General Hospital Research Institute, Rochester General Hospital, New York.
David
D
Verhoeven
Rochester General Hospital Research Institute, Rochester General Hospital, New York.
Qingfu
Q
Xu
Rochester General Hospital Research Institute, Rochester General Hospital, New York.
Michael E
ME
Pichichero
D000208:Acute Disease; D056704:Adaptive Immunity; D002675:Child, Preschool; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006193:Haemophilus influenzae / Q000302:isolation & purification*; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology; D010252:Paramyxoviridae / Q000302:isolation & purification*; D011446:Prospective Studies; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification*; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology
D006684:HLA-DR Antigens; C495344:TLR3 protein, human; C495348:TLR7 protein, human; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7
acute otitis media; adaptive immune responses; otitis-prone children; parainfluenza virus; respiratory syncytial virus