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New insight into an old concept: role of immature erythroid cells in immune pathogenesis of neonatal infection.

Elahi S - Front Immunol (2014)

Bottom Line: Herein, I provide evidence that the reduced ability to mount a protective immune response to pathogens is not due to an inherent immaturity of neonatal immune cells but instead the functions of these immune cells are actively suppressed by CD71(+) erythroid cells.In addition to these distinct features, CD71(+) erythroid cells impact digestive health by preventing excessive inflammation following the sudden transition from a sterile in utero setting to excessive colonization with commensals in the external environment.Ongoing research in identifying the beneficial and/or detrimental effects of immature erythrocytes on immune responses may serve to enhance protective newborn immune responses to infection and enable better vaccination strategies for the young to be designed.

View Article: PubMed Central - PubMed

Affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , Canada.

ABSTRACT
Newborns are exceedingly susceptible to infection. However, very little is known about what governs the immunological differences seen in early life that result in extreme vulnerability to infection, nor how this changes during infancy. Herein, I provide evidence that the reduced ability to mount a protective immune response to pathogens is not due to an inherent immaturity of neonatal immune cells but instead the functions of these immune cells are actively suppressed by CD71(+) erythroid cells. Furthermore, the role of CD71(+) erythroid cells in host defense against infection is examined. CD71(+) erythroid cells are enriched in newborns and have distinctive immunosuppressive properties that leave them vulnerable to infection. Moreover, immature erythroid cells possess exclusive immunomodulatory properties and may play a role in immune ontogeny. In addition to these distinct features, CD71(+) erythroid cells impact digestive health by preventing excessive inflammation following the sudden transition from a sterile in utero setting to excessive colonization with commensals in the external environment. Ongoing research in identifying the beneficial and/or detrimental effects of immature erythrocytes on immune responses may serve to enhance protective newborn immune responses to infection and enable better vaccination strategies for the young to be designed.

No MeSH data available.


Related in: MedlinePlus

Proposed mechanisms of CD71+ erythroid cells-induced gut immune-regulation in full term versus preterm newborns. In full terms, enriched CD71+ erythroid cells generate a suppressed immune environment by regulatory and Th2 type cytokine in the intestine, which down-regulates TLR expression, maintains symbiosis and intestinal integrity. In contrast, lower and/or dysfunctional CD71+ erythroid cells in preterm disrupts normal immune homeostasis in the gut leading to a switch from a suppressed environment to a pro-inflammatory state, up-regulates TLR expression, dysbiosis, and pathological alterations associated with NEC.
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Figure 3: Proposed mechanisms of CD71+ erythroid cells-induced gut immune-regulation in full term versus preterm newborns. In full terms, enriched CD71+ erythroid cells generate a suppressed immune environment by regulatory and Th2 type cytokine in the intestine, which down-regulates TLR expression, maintains symbiosis and intestinal integrity. In contrast, lower and/or dysfunctional CD71+ erythroid cells in preterm disrupts normal immune homeostasis in the gut leading to a switch from a suppressed environment to a pro-inflammatory state, up-regulates TLR expression, dysbiosis, and pathological alterations associated with NEC.

Mentions: Of note, the cytokine profile toward Th1, Th2, or Th17 predominance has been shown to contribute to chronic inflammatory bowel disease in human beings and animal models and likely influences TLRs expression in the intestinal mucosa (44). Although, TLR signaling is tightly regulated and coordinates homeostatic responses to commensal bacteria (45, 46), Th2 cytokines, and predominantly IL-4, and it appears to dampen TLR expression and function in human intestinal epithelial cells (IECs) (45). Therefore, it is possible to predict that the selective accumulation of CD71+ cells may explain the apparent differences observed in the type of immune responses (Th2) generated in neonates (29). Consequently, the Th2 phenotype down-regulates expression of TLRs in order to quench the excessive inflammation induced by sudden colonization with commensal bacteria after parturition (Figure 3). It has been reported that the premature intestinal environment is predisposed to exaggerated inflammatory responses, possibly leading to NEC (47, 48). Because host-mediated inflammation alone is sufficient to perturb the composition of the intestinal microbiota, it eliminates a subset of bacteria while supporting the growth of others (40). With this concept, it is plausible to hypothesize that the hyperinflammation leading to destruction of the intestine seen in NEC in premature infants might take place because the immune system of the infant overreacts to the commensal colonization as the immunosuppressive CD71+ erythroid cells has yet to be developed. Specifically, nucleated erythroid cells can produce cytokines that contribute to the Th1/Th2 balance, an important one being IL-6 (29). As IL-6 has pro-resolution properties, including inhibition of neutrophil migration (49), this polarization may serve to reduce the risk of an excessive pro-inflammatory/Tn1 response during the initial colonization of the gut with microbiota. Further studies are required to determine whether CD71-depletion in full term newborn results is dysbiosis or any histopathological alterations such as increased intestinal permeability and subsequent bacterial translocation.


New insight into an old concept: role of immature erythroid cells in immune pathogenesis of neonatal infection.

Elahi S - Front Immunol (2014)

Proposed mechanisms of CD71+ erythroid cells-induced gut immune-regulation in full term versus preterm newborns. In full terms, enriched CD71+ erythroid cells generate a suppressed immune environment by regulatory and Th2 type cytokine in the intestine, which down-regulates TLR expression, maintains symbiosis and intestinal integrity. In contrast, lower and/or dysfunctional CD71+ erythroid cells in preterm disrupts normal immune homeostasis in the gut leading to a switch from a suppressed environment to a pro-inflammatory state, up-regulates TLR expression, dysbiosis, and pathological alterations associated with NEC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129624&req=5

Figure 3: Proposed mechanisms of CD71+ erythroid cells-induced gut immune-regulation in full term versus preterm newborns. In full terms, enriched CD71+ erythroid cells generate a suppressed immune environment by regulatory and Th2 type cytokine in the intestine, which down-regulates TLR expression, maintains symbiosis and intestinal integrity. In contrast, lower and/or dysfunctional CD71+ erythroid cells in preterm disrupts normal immune homeostasis in the gut leading to a switch from a suppressed environment to a pro-inflammatory state, up-regulates TLR expression, dysbiosis, and pathological alterations associated with NEC.
Mentions: Of note, the cytokine profile toward Th1, Th2, or Th17 predominance has been shown to contribute to chronic inflammatory bowel disease in human beings and animal models and likely influences TLRs expression in the intestinal mucosa (44). Although, TLR signaling is tightly regulated and coordinates homeostatic responses to commensal bacteria (45, 46), Th2 cytokines, and predominantly IL-4, and it appears to dampen TLR expression and function in human intestinal epithelial cells (IECs) (45). Therefore, it is possible to predict that the selective accumulation of CD71+ cells may explain the apparent differences observed in the type of immune responses (Th2) generated in neonates (29). Consequently, the Th2 phenotype down-regulates expression of TLRs in order to quench the excessive inflammation induced by sudden colonization with commensal bacteria after parturition (Figure 3). It has been reported that the premature intestinal environment is predisposed to exaggerated inflammatory responses, possibly leading to NEC (47, 48). Because host-mediated inflammation alone is sufficient to perturb the composition of the intestinal microbiota, it eliminates a subset of bacteria while supporting the growth of others (40). With this concept, it is plausible to hypothesize that the hyperinflammation leading to destruction of the intestine seen in NEC in premature infants might take place because the immune system of the infant overreacts to the commensal colonization as the immunosuppressive CD71+ erythroid cells has yet to be developed. Specifically, nucleated erythroid cells can produce cytokines that contribute to the Th1/Th2 balance, an important one being IL-6 (29). As IL-6 has pro-resolution properties, including inhibition of neutrophil migration (49), this polarization may serve to reduce the risk of an excessive pro-inflammatory/Tn1 response during the initial colonization of the gut with microbiota. Further studies are required to determine whether CD71-depletion in full term newborn results is dysbiosis or any histopathological alterations such as increased intestinal permeability and subsequent bacterial translocation.

Bottom Line: Herein, I provide evidence that the reduced ability to mount a protective immune response to pathogens is not due to an inherent immaturity of neonatal immune cells but instead the functions of these immune cells are actively suppressed by CD71(+) erythroid cells.In addition to these distinct features, CD71(+) erythroid cells impact digestive health by preventing excessive inflammation following the sudden transition from a sterile in utero setting to excessive colonization with commensals in the external environment.Ongoing research in identifying the beneficial and/or detrimental effects of immature erythrocytes on immune responses may serve to enhance protective newborn immune responses to infection and enable better vaccination strategies for the young to be designed.

View Article: PubMed Central - PubMed

Affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , Canada.

ABSTRACT
Newborns are exceedingly susceptible to infection. However, very little is known about what governs the immunological differences seen in early life that result in extreme vulnerability to infection, nor how this changes during infancy. Herein, I provide evidence that the reduced ability to mount a protective immune response to pathogens is not due to an inherent immaturity of neonatal immune cells but instead the functions of these immune cells are actively suppressed by CD71(+) erythroid cells. Furthermore, the role of CD71(+) erythroid cells in host defense against infection is examined. CD71(+) erythroid cells are enriched in newborns and have distinctive immunosuppressive properties that leave them vulnerable to infection. Moreover, immature erythroid cells possess exclusive immunomodulatory properties and may play a role in immune ontogeny. In addition to these distinct features, CD71(+) erythroid cells impact digestive health by preventing excessive inflammation following the sudden transition from a sterile in utero setting to excessive colonization with commensals in the external environment. Ongoing research in identifying the beneficial and/or detrimental effects of immature erythrocytes on immune responses may serve to enhance protective newborn immune responses to infection and enable better vaccination strategies for the young to be designed.

No MeSH data available.


Related in: MedlinePlus