Abstract
BackgroundThe innate immune responses of neonates differ dramatically from those of adults. Here we examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection.ResultsWe demonstrate that virus replication proceeds indistinguishably in all age groups (inoculated at 1, 2, 3 and 4 weeks of age), although inflammatory responses vary in extent and character. Some of the biochemical mediators detected varied minimally with age at inoculation. Most of the mediators evaluated demonstrated elevated expression over baseline correlating directly with age at the time of virus inoculation. Among the latter group are CCL2, CCL3, and IFN-γ, all cytokines previously associated with PVM-induced inflammatory pathology in mature mice. Likewise, we detect neutrophil recruitment to lung tissue in all age groups, but recruitment is most pronounced among the older (3 - 4 week old) mice. Interestingly, all mice exhibit failure to thrive, lagging in expected weight gain for given age, including the youngest mice that present little overt evidence of inflammation.ConclusionsOur findings among the youngest mice may explain in part the phenomenon of atypical or minimally symptomatic respiratory infections in human neonates, which may be explored further with this infection model.
Highlights
The innate immune responses of neonates differ dramatically from those of adults
We report our findings on virus replication as well as biochemical and cellular inflammatory responses to acute pneumonia virus of mice (PVM) infection in this critical target population, which reveal an intriguing parallel between neonatal PVM infection and atypical respiratory syncytial virus (RSV) infection in newborn humans
Others included in Group II include CCL2, CCL3, CXCL1, CXCL9 and CXCL10, which are all chemokines implicated in inflammatory pathology in response to PVM infection
Summary
The innate immune responses of neonates differ dramatically from those of adults. We examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection. Most aspects of immune function are distinct in newborn infants when compared to adults of a given species. Innate immune responses among mammalian neonates are typically skewed toward the production of Th2-type cytokines; the relatively limited capacity for a Th1 response (TNF, IL-12, IFNg) has been interpreted as functionally adaptive, serving to protect the developing fetus and neonate against hyperinflammation and/or destructive responses to maternal tissues (reviewed in [1,2,3,4]). As part of our ongoing interest in innate immune responses to respiratory viral pathogens, we have characterized the pneumonia virus of mice (PVM) infection Neonates are vulnerable to infectious diseases, as they are without adequate defense against pathogenic bacteria and viruses, and, if infected, they are potentially predisposed to allergic sequelae [5,6].
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