Abstract
Infant’s immune system cannot control infection or respond to vaccination as efficiently as older individuals, a phenomenon that has been attributed to immunological immaturity. Recently, we challenged this notion and proposed the presence of actively immunosuppressive and physiologically enriched CD71+ erythroid cells in neonates. Here we utilized Bordetella pertussis, a common neonatal respiratory tract pathogen, as a proof of concept to investigate the role of these cells in adaptive immunity. We observed that CD71+ cells have distinctive immunosuppressive properties and prevent recruitment of immune cells to the mucosal site of infection. CD71+ cells ablation unleashed induction of B. pertussis-specific protective cytokines (IL-17 and IFN-γ) in the lungs and spleen upon re-infection or vaccination. We also found that CD71+ cells suppress systemic and mucosal B. pertussis-specific antibody responses. Enhanced antigen-specific adaptive immunity following CD71+ cells depletion increased resistance of mice to B. pertussis infection. Furthermore, we found that human cord blood CD71+ cells also suppress T and B cell functions in vitro. Collectively, these data provide important insight into the role of CD71+ erythroid cells in adaptive immunity. We anticipate our results will spark renewed investigation in modulating the function of these cells to enhance host defense to infections in newborns.
Highlights
Neonates are highly susceptible to disseminated and fetal infections[1]
It is unclear whether the diminished responsiveness to mount pathogen-specific T cell and B cell responses is due to an inherent immune cell-intrinsic defects of effector cells and antigen presenting cells (APCs), or because the function of these cells is actively suppressed by suppressor cells that are present during gestation or immediately after parturition
As a proof of concept, using 6 day old newborn mice, we recently showed that neonatal CD71+ cells are able to abrogate innate immune responses against B. pertussis infection
Summary
Neonates are highly susceptible to disseminated and fetal infections[1]. The clear example of this is HIV infection, which rapidly progresses to AIDS in newborns in the absence of antiretroviral therapy[2, 3]. Newborns have limited immunological memory reflecting the fetal life, where exposure to antigens is highly restricted to non-inherited maternal alloantigens (NIMA)[7] This lack of immunological memory increases their susceptibility to infectious diseases which accounts for 40% of the annual 3 million worldwide neonatal mortality[8]. It has become progressively clear that neonatal adaptive immune responses exhibit a great deal of variability ranging from lack of response to fully functional[5] This variability may explain presence of some immunological factors or non-immune cells in newborns that may impact their immune responses. We showed that the functionality of adoptively transferred adult CD11b+ granulocyte/macrophage and CD11c+ dendritic cells wiped out in the newborn mouse in response to Listeria monocytogenes infection, whereas the functionality of donor neonatal CD11b+CD11c+ cells into the adult mouse was restored[12] This further demonstrates the immunosuppressive nature of the neonatal environment. Our results here for the first time demonstrate that CD71+ cells in addition to innate immunity suppress adaptive immunity in the newborn
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