[NATURE] Neonatal RSV infection associated with increased susceptibility to allergic asthma

Image: CC/CDC. EM micrograph of RSV

Primer:  Previous studies have demonstrated a strong association between recurrent Respiratory Syncytial Virus (RSV) infections in neonates and the development of asthma later in life. In some populations, as high as 40-50% of those infected with RSV go on to eventually develop asthmatic symptoms. Unfortunately, little is currently known about the specific pathologic processes underlying this association.    

This [experimental] study: Published on Sept. 9^th in Nature Medicine used a murine model to compare T-regulatory (T-reg) cell function in infants with multiple early RSV infections to infection-free controls. The study evaluated the effects of RSV on the development of maternally transferred immune tolerance in mice pups using the model antigen ovalbumin (OVA). In the study, mice pups were exposed to OVA containing breast milk and then infected with RSV at weeks 3, 4, and 5 after weaning in order to mimic recurrent infections in humans. Upon subsequent challenge with aerosol OVA on week 7, the RSV infected mice failed to develop tolerance, resulting in an allergic response to OVA. Uninfected pups developed normal tolerance and did not mount an allergic response. Allergic responses in RSV infected pups were associated with IL-4 receptor α (IL-4Rα) dependent T-reg cell dysfunction whereby T-reg cells lost their suppressive ability and developed a T helper cell type 2 (Th-2) phenotype. The abnormal T-reg cells were shown to promote increased airway cellular infiltration and mucus production via increased production of the Th-2 specific inflammatory cytokines IL-5 and IL-13, leading to increased central airway resistance and subsequent asthmatic response upon antigenic stimulation.

In sum: Recurrent RSV infection in neonatal mice is associated with impaired immune tolerance and the development of allergic asthma. RSV infection appears to alter T-reg cell function promoting a Th-2 like phenotype in T-reg cells resulting in airway hypersensitivity and asthma induction.  If confirmed by independent human trials, the results could signal a greater role for neonatal viral infections in the pathogenesis of asthma and other immunologic hypersensitivity disorders. In addition, treatment and preventive strategies aimed at inhibiting RSV mediated T-reg to Th-2 conversion may help to reduce the incidence and severity of asthma in children. More clinical research is needed in this area. Major limitations of the study included the presence of species-specific differences in immune function and regulation between mice and humans and the possibility of pathogenic confounds.

Click to read in Nature Medicine

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