Immunological response to cytomegalovirus in congenitally infected neonates

Abstract

Summary Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide and occurs as a result of transplacental transmission of the virus. The human neonate is highly susceptible to infection due to a combination of immaturity of the immune system and antigenic inexperience. This study uses the in vivo model of congenital CMV to examine both the humoral and cell-mediated immune responses in vertically infected neonates and their mothers. Ten pairs of matched neonates and their mothers were evaluated for specific IgM responses to three immunodominant CMV antigens: pp38 (pUL80a), pp52 (pUL44) and pp150 (pUL32). In contrast to conventional enzyme immunoassay (EIA) testing for CMV-specific IgM, which found five of the mothers and four of the neonates to be positive, Western immunoblotting showed all 10 adults and nine newborns to be positive. Eight mothers and nine newborns had serological evidence of primary infection. All neonates showed a response to pp38, an assembly protein, nine responded to the pp52 immediate early antigen but only four had reactivity to the pp150 tegument associated protein. Of the mothers, eight had pp38 reactivity, 10 showed a response to the pp52 antigen and seven to the pp150 antigen. T cell-mediated immunity was assessed by measuring cytokines using a multiplex microarray assay. Levels of interferon (IFN)-γ were high in both groups [mean ± standard error of the mean (s.e.m.): neonates = 657 ± 238 pg/ml, mothers = 1072 ± 677 pg/ml, pNS]; however, neonates had significantly higher levels of interleukin (IL)-8 (316 ± 136 pg/ml versus 48 ± 28 pg/ml, P < 0·005). Similar levels of IL-2, IL-7, IL-10 and IL-12 were measured in both groups, but levels of IL-1α, IL-1β, IL-4, IL-6 and tumour necrosis factor (TNF)-α were either absent or low. In response to CMV, neonates and adults mount a predominant T helper 1 (Th1) response, as evidenced by the presence of IL-2, IL-8, IL-12 and IFN-γ with concomitant lack of IL-4. These findings suggest that the neonate, when presented with infection in utero, is capable of mounting an individual response; however, the lower IFN-γ and higher IL-8 levels suggest reduced immune responsiveness when compared to their adult counterparts.