Abstract
Antigen capturing at the periphery is one of the earliest, crucial functions of antigen-presenting cells (APCs) to initiate immune responses. Langerhans cells (LCs), the epidermal APCs migrate to draining lymph nodes (DLNs) upon acquiring antigens. An arsenal of endocytic molecules is available to this end, including lectins and pathogen recognition receptors (PRRs). However, cutaneous LCs are poorly defined in the early neonatal period. We assessed endocytic molecules expression in situ: Mannose (CD206)-, Scavenger (SRA/CD204)-, Complement (CD2l, CDllb)-, and Fc-Receptors (CD16/32, CD23) as well as CD1d, CD14, CD205, Langerin (CD207), MHCII, and TLR4 in unperturbed epidermal LCs from both adult and early neonatal mice. As most of these markers were negative at birth (day 0), LC presence was revealed with the conspicuous, epidermal LC-restricted ADPase (and confirmed with CD45) staining detecting that they were as numerous as adult ones. Unexpectedly, most LCs at day 0 expressed CD14 and CD204 while very few were MHCII+ and TLR4+. In contrast, adult LCs lacked all these markers except Langerin, CD205, CD11b, MHCII and TLR4. Intriguingly, the CD204+ and CD14+ LCs predominant at day 0, apparently disappeared by day 4. Upon cutaneous FITC application, LCs were reduced in the skin and a CD204+MHCII+FITC+ population with high levels of CD86 subsequently appeared in DLNs, with a concomitant increased percentage of CD3+CD69+ T cells, strongly suggesting that neonatal LCs were able both to ferry the cutaneous antigen into DLNs and to activate neonatal T cells in vivo. Cell cycle analysis indicated that neonatal T cells in DLNs responded with proliferation. Our study reveals that epidermal LCs are present at birth, but their repertoire of endocytic molecules and PRRs differs to that of adult ones. We believe this to be the first description of CDl4, CD204 and TLR4 in neonatal epidermal LCs in situ. Newborns’ LCs express molecules to detect antigens during early postnatal periods, are able to take up local antigens and to ferry them into DLNs conveying the information to responsive neonatal T cells.
Highlights
Stages of life are related to high susceptibility to infections, which has been attributed to an immature or ineffective immune system, the scarce available research on the immunological competence of newborns is frequently contradictory [1]
In order to evaluate in situ the phenotype of Langerhans cells (LC) in newborn and adult mice, we probed the epidermis for the expression of molecules putatively related with the function of antigen uptake or recognition, we included several putative pattern recognition receptor (PRR) or endocytic molecules: CD1d, CD206, TLR4; complement receptor molecules: CD11b and CD21; Fc-Receptors: CD16/CD32 and CD23; and CD14 and CD204 (Figures 1B,C)
Several studies have reported that murine fetal epidermis contains ADPase+CD11b+F4/80+CD32+CD115+CX3CR1+MHCII− CD205− CD207− CD90− CD3− dendritic epidermal leukocytes, distinct mice strains may have an impact on these differences [25, 26, 29, 41, 42]
Summary
Stages of life are related to high susceptibility to infections, which has been attributed to an immature or ineffective immune system, the scarce available research on the immunological competence of newborns is frequently contradictory [1]. While most studies in neonates deal with adaptive immunity, reports on cells of innate responses are scarce [1]. Murine and human neonatal lymphocytes are functionally different from adults and it is generally accepted that T cells in neonates are biased to a Th2 cytokine profile [2,3,4]. It has been shown that under adequate stimulation, early neonates are competent to mount adult-like adaptive immune responses [5,6,7,8]. There are crucial factors that in early life can determine either dampened or protective immunity, including the dose of antigen, type of adjuvant and type of cells presenting antigen to naïve T cells [9,10,11]
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