Decreased Toll-Like Receptor-4/Myeloid Differentiation Factor 88 Response Leads to Defective Interleukin-1β Production in Term Low Birth Weight Newborns

Singh, Vikas Vikram; Chauhan, Sudhir Kumar; Rai, Richa; Kumar, Ashok; Rai, Geeta

doi:10.1097/inf.0000000000000416

Cited by 6 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…expression and impaired cytokine response upon LPS stimulation [Förster-Waldl et al, 2005]. Similar findings are reported for LBW neonates [Singh et al, 2014]. The extent of downregulation in TLR signaling cascade appears to be dictated by the degree of prematurity, as neutrophils from extremely premature (birth weight <1,000 g) neonates have a significantly reduced surface expression of not only TLR-4 but also TLR-2, CD14, and MD-2 [Tissières et al, 2012].…”

supporting

confidence: 56%

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

Doğan

Karagenc

Esmen

et al. 2023

Cells Tissues Organs

View full text Add to dashboard Cite

Mouse fetuses generated by in vitro embryo culture and embryo transfer exhibit impaired lung development, altered composition of pulmonary epithelial cells associated with downregulation of several genes involved in lung development and toll-like receptor (TLR) signaling pathway. The aims of the present study were to determine the expression of all TLRs and to examine if the expression of TLRs, along with genes involved in TLR signaling pathway, is altered in the lung tissue of mouse fetuses generated through embryo culture and embryo transfer. Two experimental (EGs) and one control (CG) group were included in the study. Embryos cultured at 5% CO2-95% air for 95 h or less than 24 h were transferred to pseudo-pregnant females to obtain fetuses comprising EGin vitro (n = 18) and EGin vivo (n = 18), respectively. Fetuses obtained from naturally ovulating females on day 18 of pregnancy served as the CG (n = 18). Western blot and immunohistochemistry were used to determine the expression of TLR proteins. The expression of transcripts encoding TLRs, and the genes involved in TLR signaling pathway (Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos), was determined using qRT-PCR. While all TLRs were expressed by cells lining the bronchial/bronchiolar epithelium of lung tissues in all groups, some of the TLRs were expressed in a specific pattern. When compared to CG, the expression of transcripts encoding TLR-2, -3, -4, -5, -7, -8, -9, -12, -13, Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos was significantly downregulated in both EGs. It appears that stress imposed on embryos at preimplantation stages of development is associated with downregulation of TLRs, along with some of the genes involved in TLR signaling pathway, in the lung tissue during the perinatal period. It remains to be determined if downregulation of TLRs, along with the genes involved in TLR signaling pathway, has any functional consequences in the adult lung tissue.

show abstract

supporting

confidence: 56%

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

Doğan

Karagenc

Esmen

et al. 2023

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…In contrast to TLR2 which requires MYD88 for signal transduction, TLR4 can alternatively engage TRAM/TRIF [5, 32]. We observed that MYD88, a protein critically involved in TLR2 signalling, is abundantly expressed and stands by to drive downstream signalling in CBMO (Fig 3B).…”

Section: Discussionmentioning

confidence: 76%

“…albicans in healthy full-term neonatal compared to adults. It seems that innate immunity is differentially regulated among neonatal subsets, depending on gestational age and birth weight, involving pattern recognition receptor- and TLR4-signalling [31, 32]. …”

Section: Discussionmentioning

confidence: 99%

Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida albicans

Dreschers

Saupp

Hornef³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

BackgroundInvasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO).HypothesisPhagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses.MethodsThe ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor).ResultsPhagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of TLR2 and consecutive phosphorylation of MAP kinase P38 and expression of TNF-α, which were stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs PBMO).ConclusionOur data suggest direct involvement of TLR2-signalling in C. albicans-induced PICD in monocytes and an alteration of this pathway in CBMO.

show abstract

“…It is essential for the perception of MAMP and presentation to TLR. When TLR-MYD88 expression is down-regulated, infants are more susceptible to serious infection 34) . Excessive TLR4 signaling regulates apoptosis, proliferation, and migration of enterocytes, microcirculatory perfusion, and other effects.…”

Section: Microbial Role In Nec Developmentmentioning

confidence: 99%

Fetal and preterm infant microbiomes: a new perspective of necrotizing enterocolitis

Choi

Song

2017

Korean J Pediatr

View full text Add to dashboard Cite

Necrotizing enterocolitis (NEC) is a devastating condition of hospitalized preterm infants. Numerous studies have attempted to identify the cause of NEC by examining the immunological features associated with pathogenic microorganisms. No single organism has proven responsible for the disease; however, immunological studies are now focused on the microbiome. Recent research has investigated the numerous bacterial species residing in the body and their role in diseases in preterm infants. The timing of initial microbial colonization is a subject of interest. The microbiome appears to transfer from the mother to the newborn, as well as to the fetus. Cross-talk between the fetus and fetal microbiome takes place continuously to generate a unique immune system. This review examined the transfer of the microbiome to the human fetus, and its potential relationship with NEC.

show abstract

Decreased Toll-Like Receptor-4/Myeloid Differentiation Factor 88 Response Leads to Defective Interleukin-1β Production in Term Low Birth Weight Newborns

Cited by 6 publications

References 28 publications

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida albicans

Fetal and preterm infant microbiomes: a new perspective of necrotizing enterocolitis

Contact Info

Product

Resources

About