Speaker
Description
The morbidity and mortality of newborn infants from influenza infections is low compared to older children and adults. It is largely unclear what reprogramming of immunity causes the higher susceptibility to severe influenza infections with increasing age.
We challenged human respiratory and innate immune cells from healthy newborns and adults with the H1N1/California/04/2009 virus. Next to detailed virus-addressing studies we performed global transcriptomic analyses using a variety of state-of-the-art computational methods. While no differences could be observed regarding viral infectibility and progeny, the inflammatory response of neonatal primary airway epithelial cells, macrophages and monocytes upon influenza A virus (IAV) infection was generally dampened compared to adults. A system biology approach revealed that the differential anti-IAV response of human monocytes was primarily linked to differential programming in newborns and adults at baseline. Genes related to antigen presentation and myeloid differentiation were in fact less inducible but shaped the age-dependent anti-IAV response by opposing and strong basal expression differences. In contrast, IFN response genes and energy supply-related metabolic pathways were comparably strong induced but in neonates parallelly shifted to significantly lower expression levels than in adults suggesting training with increasing age.
We conclude that the course and outcome of influenza infections is less driven by the viral load but determined by the host’s inflammatory response. The priming of IFN response and metabolic gene modules during environmental adaptation might represent the critical determinant of how the host’s responsivity to influenza infections evolves later in life.
| Choose primary session | Innate Immunity |
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