Infant Immune Response to Respiratory Viral Infections

Abstract

Of all respiratory viruses that affect infants, respiratory syncytial virus (RSV) and rhinovirus (RV) represent the leading pathogens causing acute disease (bronchiolitis) and are associated with the development of recurrent wheezing and asthma. The immune system in infants is still developing, and several factors contribute to their increased susceptibility to viral infections. These factors include differences in pathogen detection, weaker interferon responses, lack of immunologic memory toward the invading pathogen, and T-cell responses that are balanced to promote tolerance and restrain inflammation. These aspects are reviewed here with a focus on RSV and RV infections.

Keywords: Adaptive immune response; Innate immunity; RSV; Rhinovirus.

Figure 1.. CD4+ T helper cell differentiation and signaling.

CD4+ T-cells differentiate into specific T-helper subsets upon activation of T-cell receptors including: Th1, Th2, Th17, T-regs and T follicular helper (Tfh) cells, which are defined by their function and cytokine milieu.

Figure 2.. Age at the time of infection influences the host immune response to respiratory syncytial virus (RSV) and rhinovirus (RV) infection.

(A) Immune pathways activated or suppressed during RSV lower respiratory tract infection (LRTI) were compared between 20 infants < 6 months of age and 17 children with RSV LRTI 6–24 months of age (upper panel). Both groups had similar clinical disease severity scores (CDSS). Colored spots represent the percentage of significantly over-expressed (red) or under-expressed (blue) transcripts within a module, and the number included in the dots are the percentage of over or underexpressed transcripts. Blank modules demonstrate no significant differences in expression. The middle panel summarizes the percentage of over and underexpressed transcripts according to the two age groups and in relation to the overall RSV signature. The lower panel further illustrates in a spider graph format the differences in immune responses between the two age groups. (B) Infants with RV LRTI (less than 6 months; n=12 and 6–24 months: n=8) revealed fewer differences in host responses according to age. Horizontal bars illustrate the proportion of over-and under-expressed modules in infants (less than 6 months) and children 6–24 months of age in relation to the global influenza and RV signature. These differences are further illustrated in a spider graph format representing the per-module median expression values of the significant different modules between the two age groups. Adapted from Mejias A, Dimo B, Suarez NM, et al. Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection. PLoS Med 2013;10(11):e1001549; with permission.