Erythroid Suppressor Cells Compromise Neonatal Immune Response against Bordetella pertussis

Abstract

Newborns are highly susceptible to infection. The underlying mechanism of neonatal infection susceptibility has generally been associated with neonatal immune cell immaturity. In this study, we challenged this notion and built upon our recent discovery that neonates are physiologically enriched with erythroid TER119CD71 cells (Elahi et al. 2013. 504: 158-162). We have used, a common neonatal respiratory tract infection, as a proof of concept to investigate the role of these cells in newborns. We found that CD71 cells have distinctive immune-suppressive properties and suppress innate immune responses against infection. CD71 cell ablation unleashed innate immune response and restored resistance to infection. In contrast, adoptive transfer of neonatal CD71 cells into adult recipients impaired their innate immune response to infection. Enhanced innate immune response to was characterized by increased production of protective cytokines IFN-γ, TNF-α, and IL-12, as well as recruitment of NK cells, CD11b, and CD11c cells in the lung. Neonatal and human cord blood CD71 cells express arginase II, and this enzymatic activity inhibits phagocytosis of in vitro. Thus, our study challenges the notion that neonatal infection susceptibility is due to immune cell-intrinsic defects and instead highlights active immune suppression mediated by abundant CD71 cells in the newborn. Our findings provide additional support for the novel theme in neonatal immunology that immunosuppression is essential to dampen robust immune responses in the neonate. We anticipate that our results will spark renewed investigation in modulating the function of these cells and developing novel strategies for enhancing host defense to infections in newborns.

CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

“…A previous report showed that the depletion of CD71+ erythroid cells in term-derived cord blood mononuclear cells unleashes the expression of inflammatory cytokines by myeloid cells [21, 73]. Yet, our data are consistent with previous observations demonstrating that fetal monocyte activation, as assessed by the expression of IL-6, is associated with the process of labor [74].…”

CD71+erythroid cells exacerbate HIV-1 infection by reactive oxygen species and trans-infect HIV to CD4+T cells

“…In agreement with our previous reports (6,15), here we show that CECs are physiologically abundant in the human umbilical cord blood, and placental tissues while they are almost absent in the peripheral blood of healthy adults ( Fig. 1A and B).…”

“…1A and B). Since we have reported that CECs have immunomodulatory properties (6,8,15), their impact on HIV-1 infection in CD4 + T cells was evaluated in an HIV-1 ex vivo infection assay. Cord blood CD4 + T cells were isolated and made more permissible to HIV-1 infection by in vitro culture with exogenous IL-2 and PHA stimulation (23).…”

“…However, in recent years mounting evidence indicate a direct and important role for these cells in innate immunity and inflammation (3,4). In addition to mature RBCs, a wide range of immunomodulatory functions have been assigned to their immature counterparts (5)(6)(7)(8). One important immunomodulatory feature of human RBCs is their tendency to bind to a wide range of chemokines.…”

“…It is worth noting that under certain physiological or pathological conditions, immature red blood cells can be seen in the periphery of adults (11)(12)(13). For instance, conditions such as anemia, pregnancy, chronic infection and late stage cancer result in a process called extramedullary erythropoiesis in liver and/or spleen, which results with the presence of immature red blood cells in the periphery (6,10,11,14).…”