Pattern Recognition Receptors and Genetic Risk for RSV Infection: Value for Clinical Decision-Making?

Respiratory syncytial virus (RSV) causes respiratory tract infections, especially among young infants. Practically, all infants are infected during epidemics and the clinical presentation ranges from subclinical to fatal infection. Known risk factors for severe RSV infection include prematurity, age of <2 months, underlying chronic lung or heart diseases, serious neurological or metabolic disorders, immune deficiency (especially a disorder of cellular immunity), crowded living conditions, and indoor smoke pollution. Twin studies indicate that host genetic factors affect susceptibility to severe RSV infection. Pattern recognition receptors (PRRs) are the key mediators of the innate immune response to RSV In the distal respiratory tract, RSV is recognized by the transmembrane Toll-like receptor 4 (TLR4) and adapter proteins, which lead to production of proinflammatory cytokines and subsequent activation of the adaptive immune response. Surfactant proteins A and D are able to bind both RSV and TLR4, modulating the inflammatory response. Genetic variations in TLR4, SP-A, and SP-D have been associated with the risk of severe RSV bronchiolitis, but the results have varied between studies. Both the homozygous hyporesponsive 299Gly genotype of TLR4 and the non-synonymous SP-A and SP-D polymorphism influence the presentation of RSV infection. The reported relative risks associated with these markers are not robust enough to justify clinical use. However, current evidence indicates that innate immune responses including pattern recognition receptors (PRRs) and other components in the distal airways and airspaces profoundly influence the innate immune responses, playing a key role in host resistance to RSV in young infants. This information is useful in guiding efforts to develop better means to identity the high-risk infants and to treat this potentially fatal infection effectively. Pediatr Pulmonol. 2011; 46:101-110. (C) 2011 Wiley-Liss, Inc.