scholarly journals Toll-Like Receptor Signaling in the Establishment and Function of the Immune System

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1374
Author(s):  
Jahnavi Aluri ◽  
Megan A. Cooper ◽  
Laura G. Schuettpelz
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
Cell Types ◽  
Tlr Signaling ◽  
Inborn Errors ◽  
Immune System Dysfunction ◽  
Immune System Development ◽  
And Function ◽  
Immune Defects

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in TLR signaling that lead to inborn errors of immunity.

scholarly journals Immune system development varies according to age, location, and anemia in African children

2020 ◽  
Vol 12 (529) ◽  
pp. eaaw9522 ◽  
Author(s):  
Danika L. Hill ◽  
Edward J. Carr ◽  
Tobias Rutishauser ◽  
Gemma Moncunill ◽  
Joseph J. Campo ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
High Titer ◽  
Geographical Location ◽  
Cell Types ◽  
Iron Bioavailability ◽  
Immune System Development

Children from low- and middle-income countries, where there is a high incidence of infectious disease, have the greatest need for the protection afforded by vaccination, but vaccines often show reduced efficacy in these populations. An improved understanding of how age, infection, nutrition, and genetics influence immune ontogeny and function is key to informing vaccine design for this at-risk population. We sought to identify factors that shape immune development in children under 5 years of age from Tanzania and Mozambique by detailed immunophenotyping of longitudinal blood samples collected during the RTS,S malaria vaccine phase 3 trial. In these cohorts, the composition of the immune system is dynamically transformed during the first years of life, and this was further influenced by geographical location, with some immune cell types showing an altered rate of development in Tanzanian children compared to Dutch children enrolled in the Generation R population–based cohort study. High-titer antibody responses to the RTS,S/AS01E vaccine were associated with an activated immune profile at the time of vaccination, including an increased frequency of antibody-secreting plasmablasts and follicular helper T cells. Anemic children had lower frequencies of recent thymic emigrant T cells, isotype-switched memory B cells, and plasmablasts; modulating iron bioavailability in vitro could recapitulate the B cell defects observed in anemic children. Our findings demonstrate that the composition of the immune system in children varies according to age, geographical location, and anemia status.

Perturbation of B-cell development in mice overexpressing the Bcl-2 homolog A1

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3350-3359 ◽  
Author(s):  
Peter I. Chuang ◽  
Samantha Morefield ◽  
Chien-Ying Liu ◽  
Stephen Chen ◽  
John M. Harlan ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
System Development ◽  
Cell Development ◽  
B Cell Development ◽  
Lymphoid Cells ◽  
Immune System Development ◽  
And Function

Abstract Decisions about cell survival or death are central components of adaptive immunity and occur at several levels in immune system development and function. The Bcl-2 family of homologous proteins plays an important role in these decisions in lymphoid cells. Bcl-2, Bcl-xL, and A1 are differentially expressed during B- and T-cell development, and they have shared and distinct roles in regulating cell death. We sought to gain insight into the role of A1 in immune system development and function. A murine A1-a transgene was expressed under the control of the Eμ enhancer, and mice with A1 overexpression in B- and T-cell lineages were derived. Thymocytes and early B cells in Eμ-A1 mice showed extended survival. B-lineage development was altered, with expansion of the pro–B cell subset at the expense of pre–B cells, suggesting an impairment of the pro– to pre–B-cell transition. This early B-cell phenotype resembled Eμ–Bcl-xL mice but did not preferentially rescue cells with completed V(D)J rearrangements of the immunoglobulin heavy chain. In contrast to Eμ–Bcl-2 transgenes, A1 expression in pro–B cells did not rescue pre–B-cell development in SCID mice. These studies indicate that A1 protects lymphocytes from apoptosis in vitro but that it has lineage- and stage-specific effects on lymphoid development. Comparison with the effects of Bcl-2 and Bcl-xL expressed under similar control elements supports the model that antiapoptotic Bcl-2 homologs interact differentially with intracellular pathways affecting development and apoptosis in lymphoid cells.

scholarly journals Long Chain Polyunsaturated Fatty Acids Docosahexaenoic Acid and Arachidonic Acid Supplementation in the Suckling and the Post-weaning Diet Influences the Immune System Development of T Helper Type-2 Bias Brown Norway Rat Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Dhruvesh Patel ◽  
Marnie Newell ◽  
Susan Goruk ◽  
Caroline Richard ◽  
Catherine J. Field
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
System Development ◽  
Maternal Diet ◽  
Brown Norway ◽  
Norway Rat ◽  
Adaptive Immune ◽  
Immune System Development ◽  
Brown Norway Rat

Background: Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring.Methods: Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA; n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA; n = 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA; n = 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA; n = 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses.Results: ARA + DHA maternal diet resulted in higher (p < 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytes ex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls.Conclusion: Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.

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