Human metapneumovirus (MPV) is a recently discovered pathogen that causes repeated lower
respiratory tract infections beginning in infancy. The prevalence, nature and control of human regulatory responses to MPV are unknown. In this study, we develop and optimize systems to evaluate MPV-driven
cytokine responses. Using primary culture of human PBMC from previously exposed adults, MPV-stimulated responses were directly compared with those elicited by genetically and clinically similar respiratory syncytial virus (RSV). Intense
IL-6 production was evident following culture with infectious or inactivated RSV. MPV elicited
IL-6 responses averaging 3.5-fold more intense (p < 0.001). Virus-dependent expression of
IL-11,
IL-12, IFN-alpha, and other innate immunity
cytokines differed little between MPV and RSV. When examining adaptive immunity,
RSV infection elicited strong IFN-gamma responses by all 60 adults. In marked contrast, MPV elicited IFN-gamma in a lower frequency of adults (p < 0.002) and at levels averaging 6-fold weaker (p < 0.001). These Th1-dominated responses were CD4, CD8, CD86 dependent, and were closely paralleled by strong virus-driven
IL-10 and CCL5 production. For MPV and RSV, Th2 (IL-5, IL-13) responses were sporadic, occurring in 10-40% of the population. Thus, MPV and RSV, although both ubiquitous and leading to very high levels of
infection, seroconversion, and clinically similar presentation in the population, evoke distinct innate and adaptive T cell-dependent
cytokine responses. Although both viruses yield Th1-dominated responses with strong
IL-10 and CCL5 production, MPV restimulation results in markedly more robust
IL-6 and significantly weaker adaptive
cytokine responses, in both prevalence and intensity, than does RSV.