Abstract
Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.
Highlights
Newborns and young infants have long been known to suffer higher infectious morbidity and mortality as compared to older children and adults; they often display suboptimal immune responses to vaccination [1,2]
Much of the published literature examining innate immunity has focused on pattern recognition receptors (PRR), such as Toll-like receptors (TLR), which are involved in the recognition of conserved microbial pathogen-associated molecular patterns (PAMP)
The opposite appeared to be the case for B cells; i.e. percentage of B cells was higher in mononuclear cells (MC) from 1- and 2-year olds compared to MC from cord or adult blood, respectively. cDC increased from a low at birth to adult levels by 1-year of age
Summary
Newborns and young infants have long been known to suffer higher infectious morbidity and mortality as compared to older children and adults; they often display suboptimal immune responses to vaccination [1,2]. Recognition of a specific PAMP by a specific TLR triggers events that result in the initiation of antigen uptake, processing, and presentation, as well as expression of co-stimulatory molecules and secretion of cytokine mediators Together, these responses support immediate innate effector functions, such as phagocytosis, and direct the ensuing adaptive immune response. It is important to note that innate PRRs are essential in initiating and orchestrating the immune response not just to infection, but—through recognition of adjuvants— direct the quantity, quality, and longevity of the adaptive immune response to vaccination [7]. Involved in these processes are antigenpresenting cells (APC). We conducted our analysis of innate responses to TLR stimulation in all four APC types in parallel and in the same sample
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
