Dysregulation of Expression of Immunoregulatory and Cytokine Genes and Its Association with the Immaturity in Neonatal Phagocytic and Cellular Immunity

Satwani, Prakash; Morris, Erin; Ven, Carmella van de; Cairo, Mitchell S.

doi:10.1159/000087585

Cited by 37 publications

(30 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar to our study, Thitihanyanont et al used MoDCs to demonstrate the high susceptibility of human DCs to H5N1 (24). We and others have demonstrated the deficient neonatal immune function by studying T-cells and NK-cells isolated from UCB, an enriched source of hematopoietic precursors and immune cells (16,17,23). The present study is the first to compare the effect of IAV infection on maturation of APB and UCB MoDCs.…”

Section: Discussionsupporting

confidence: 79%

Effect of Influenza A Infection on Maturation and Function of Neonatal Monocyte-Derived Dendritic Cells

Lin

Lee

2014

Viral Immunology

View full text Add to dashboard Cite

Dendritic cells (DC) are essential for the first-line innate defense against influenza infection. The greater susceptibility to severe influenza infection in young infants and neonates may be attributed in part to their defective DC function. We sought to investigate the effect of influenza A virus (IAV) infection on the maturation, apoptosis, and function of monocyte-derived dendritic cells (MoDCs) from umbilical cord blood (UCB) and compared this with responses from adult peripheral blood (APB). Our findings were as follows. First, MoDCs derived from UCB showed deficient CD40, CD80, CD86, and HLA-DR upregulation following IAV infection compared to APB MoDCs. Second, IAV induced a multiplicity of infection (MOI)-dependent increase of apoptosis in UCB MoDCs, similar to that observed with APB. Third, the ability of UCB MoDCs to uptake dextran is decreased following IAV infection. Fourth, deficient TNF-a, but not IL-6, IFN-a response was induced by IAV infection of UCB MoDCs. Fifth, the ability of UCB MoDCs to promote allogeneic CD3 T-cell proliferation is inhibited by IAV infection. Taken together, we demonstrated a differential response of UCB and APB MoDCs following IAV infection, which may contribute in part to the increased susceptibility to severe influenza infection observed in young infants and neonates.

show abstract

Section: Discussionsupporting

confidence: 79%

Effect of Influenza A Infection on Maturation and Function of Neonatal Monocyte-Derived Dendritic Cells

Lin

Lee

2014

Viral Immunology

View full text Add to dashboard Cite

show abstract

“…However, because of the relative immaturity of the immune system of neonates, one may wonder whether such immunity could be elicited in the very young. Several studies have documented the relative immaturity of the neonatal immune system, with resulting overall reductions in the secretion of proinflammatory/TH1-cell-polarizing cytokines, such as TNF, IL-1, and IFN-␥ (7,27,31,44), and increases in the production of IL-10 (7).…”

Section: Discussionmentioning

confidence: 99%

Impaired Innate and Adaptive Immunity to Streptococcus pneumoniae and Its Effect on Colonization in an Infant Mouse Model

et al. 2009

View full text Add to dashboard Cite

Streptococcus pneumoniae colonization and invasive disease peak around the third and first birthdays, respectively, and decline thereafter. While these declines are attributable in part to immunity acquired via natural exposure, maturation of innate immune responses may also be involved. A mucosally administered candidate whole-cell pneumococcal vaccine (WCV) containing killed pneumococcal antigen (WCA) plus a cholera toxin adjuvant protects against intranasal carriage of pneumococci by a mechanism that is antibody independent and CD4 ؉ TH17 cell dependent. Because infants and children are a key target population for this vaccine, we sought to evaluate the immune responses of neonatal and infant mice to S. pneumoniae and to assess whether the WCV would be effective in these mice. Like human infants, infant mice showed impaired clearance of nasopharyngeal colonization with S. pneumoniae. Macrophages from neonatal and infant mice stimulated with killed pneumococci in vitro showed significantly reduced cytokine production, including that of KC, granulocyte colony-stimulating factor, granulocytemacrophage colony-stimulating factor, macrophage chemoattractant protein 1, interleukin-6 (IL-6), IL-1␣, tumor necrosis factor alpha, and gamma interferon, whereas IL-10 expression was significantly increased compared to that in macrophages from adult mice. IL-17A production from adult immune CD4 ؉ T cells was significantly delayed when neonatal macrophages instead of adult macrophages were used as antigen-presenting cells. Moreover, whole blood from mice immunized as neonates with WCV produced significantly less IL-17A after stimulation with WCA than did blood from mice immunized as adults. Nonetheless, a single immunization of neonatal mice with WCV significantly reduced colonization density. Overall, our data suggest an impairment of both innate and acquired cellular immune responses in neonatal and infant mice. However, WCV confers a significant reduction in colonization following pneumococcal challenge, suggesting that it may still be effective in the setting of immature immune responses.

show abstract

“…As discussed earlier for neonatal monocytes, this incomplete DC maturation may be a consequence of defective responses to TLR signaling. Of interest, mRNA levels of molecules downstream with TLR4 signaling such as MAPKKK, NF-KB and TANK, are markedly decreased in LPS-stimulated CBMDDCs compared to adult MDDCs [32]. However, it is important to underline that the response to other TLRs expressed in this cellular population, TLR1, 2, 3, 6, and 8 and possibly TLR5 [33], has not yet been reported in neonate cells.…”

Section: Cord Blood Monocyte-derived Dendritic Cellsmentioning

confidence: 99%

Defective antigen-presenting cell function in human neonates

Velilla¹,

Rugeles²,

Chougnet³

2006

Clinical Immunology

152

132

View full text Add to dashboard Cite

Immaturity of the immune system has been suggested as an underlying factor for the high rate of morbidity and mortality from infections in newborns. Functional impairment of neonatal T cells is frequently quoted as the main underlying mechanism for such immaturity. However, recent studies suggest that neonatal antigen-presenting cells (APCs) also exhibit functional alterations, which could lead to secondary defects of adaptive T cell responses. In this review, we summarize what is known on the functionality of APC at birth and during early childhood. Compared to adults, neonatal APCs display markers of immaturity and produce low levels of cytokines. Multiple factors could be involved in neonatal APC alteration, such as intrinsic immaturity, defective interaction between APCs and T cells, and regulatory T cell-mediated inhibition. Characterization of the relative contribution of each mechanism is clearly needed to better understand the functional capability of the neonatal immune system.

show abstract

Dysregulation of Expression of Immunoregulatory and Cytokine Genes and Its Association with the Immaturity in Neonatal Phagocytic and Cellular Immunity

Cited by 37 publications

References 137 publications

Effect of Influenza A Infection on Maturation and Function of Neonatal Monocyte-Derived Dendritic Cells

Effect of Influenza A Infection on Maturation and Function of Neonatal Monocyte-Derived Dendritic Cells

Impaired Innate and Adaptive Immunity to Streptococcus pneumoniae and Its Effect on Colonization in an Infant Mouse Model

Defective antigen-presenting cell function in human neonates

Contact Info

Product

Resources

About