Why do some babies get sick more gravely than others by Respiratory Syncytial Virus?
TOLL RECEPTOR TYPE 4 ROLE IN PULMONARY DISEASE BY RESPIRATORY VIRUS SYNCYTIAL
While 30-70% of infants infected with respiratory syncytial virus (RSV) develop bronchiolitis, only 1% require hospitalization.
The mechanism of differential severity of the disease among healthy term infants is not fully understood. The virus titer , the inflammation and Th2 bias in the lungs , are proposed as possible explanations . The Toll-like receptor 4 ( TLR4 ) is associated with each of these disease phenotypes , but their role in pathogenesis is controversial.
The objective of this study is to determine whether the severity of RSV disease in healthy infants is determined by an interaction of TLR4 genotype with the amount of lipopolysaccharide (LPS) in the home environment and whether this interaction modifies the immune response to a Th2 made through GATA3/T-bet ratio analysis .
We performed a multicenter study which enrolled 2200 infants with bronchiolitis which analyzed the presence of two single nucleotide polymorphisms in TLR4 and its relationship with RSV infection . The mechanistic function of these molecules was confirmed in a murine model of RSV infection phenotype reproduced in the infant .
This research integrates environmental , genetic , epidemiological , viral , immunological and clinical findings affecting RSV bronchiolitis and provides a framework for translational research in the future. High ratios of GATA3/T-bet are associated with severe disease .
Pueblo Evita Hospital , Hospital de Berezategui, Hospital Mi Pueblo, Florencio Varela , and Hospital Posadas, Ciudadela, Buenos Aires , Argentina , Hospital Francés , CEMIC, Swiss Medical Center and Infant Foundation, City of Buenos Aires, Argentina. NIEHS, NIH, Research Triangle, NC, and Vanderbilt University , Department of Pediatrics, Nashville , TN , USA