Toll‐like receptors signaling network in pre‐eclampsia: An updated review

Afkham, Amir; Eghbal‐Fard, Shadi; Heydarlou, Hanieh; Azizi, Ramyar; Aghebati‐Maleki, Leili; Yousefi, Mehdi

doi:10.1002/jcp.27189

Cited by 37 publications

(20 citation statements)

References 98 publications

(228 reference statements)

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“…A fine interplay between both phases ensures a healthy pregnancy. There are numerous reports that have suggested that any dysregulation in the immune status at the materno-fetal interface due to infections are the main cause of preterm delivery, preeclampsia, gestational diabetes, miscarriage, placental malaria, and other pregnancy-related disorders (4)(5)(6)(7). There are multiple routes through which the infections can gain access to the placenta, maternal endometrium, and amniotic fluid; ascending through the genital tract and colonizing uterine cavity is the most preferred of all (8).…”

Section: Introductionmentioning

confidence: 99%

“…Pattern recognition receptors are an important element of the innate immune system since they act as a first line of defense against invading pathogens. Recognition of microorganism-originated pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs) relays the signaling cascade, leading to an increase in the expression of cytokines, chemokines, and interferons (7,9). The Toll-like receptor (TLR) family is one of the important subgroups of PRRs, and it acts as a bridge between innate and adaptive immunity.…”

Section: Introductionmentioning

confidence: 99%

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Insight Into TLR4-Mediated Immunomodulation in Normal Pregnancy and Related Disorders

2020

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Unlike organ transplants where an immunosuppressive environment is required, a successful pregnancy involves an extremely robust, dynamic, and responsive maternal immune system to maintain the development of the fetus. A specific set of hormones and cytokines are associated with a particular stage of pregnancy. Any disturbance that alters this fine balance could compromise the development and function of the placenta. Although there are numerous underlying causes of pregnancy-related complications, untimely activation of Toll-like receptors (TLR), primarily TLR4, by intrauterine microbes poses the greatest risk. TLR4 is an important Pattern Recognition Receptor (PRR), which activates both innate and adaptive immune cells. TLR4 activation by LPS or DAMPs leads to the production of pro-inflammatory cytokines via the MyD88 dependent or independent pathway. Immune cells modulate the materno-fetal interface by TLR4-mediated cytokine production, which changes at different stages of pregnancy. In most pregnancy disorders, such as PTB, PE, or placental malaria, the TLR4 expression is upregulated in immune cells or in maternal derived cells, leading to the aberrant production of pro-inflammatory cytokines at the materno-fetal interface. Lack of functional TLR4 in mice has reduced the pro-inflammatory responses, leading to an improved pregnancy, which further strengthens the fact that abnormal TLR4 activation creates a hostile environment for the developing fetus. A recent study proposed that endothelial and perivascular stromal cells should interact with each other in order to maintain a homeostatic balance during TLR4-mediated inflammation. It has been reported that depleting immune cells or supplying anti-inflammatory cytokines can prevent PTB, PE, or fetal death. Blocking TLR4 signaling or its downstream molecule by inhibitors or antagonists has proven to improve pregnancy-related complications to some extent in clinical and animal models. To date, there has been a lack of knowledge regarding whether TLR4 accessories such as CD14 and MD-2 are important in pregnancy and whether these accessory molecules could be promising drug targets for combinatorial treatment of various pregnancy disorders. This review mainly focuses on the activation of TLR4 during pregnancy, its immunomodulatory functions, and the upcoming advancement in this field regarding the improvement of pregnancy-related issues by various therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insight Into TLR4-Mediated Immunomodulation in Normal Pregnancy and Related Disorders

2020

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“…The typical receptors of HMGB1 are RAGE, TLR2, and TLR4 [14] . TLRs (except for TLR3) can activate the MyD88-dependent pathway and mediate an active in ammatory response [15] . A study on intranasal inoculation of MP in mice showed that macrophages recognized the speci c antigen of MP through its surface TLR [16] .…”

Section: Discussionmentioning

confidence: 99%

Investigation of the relationship between Community-acquired respiratory distress syndrome toxin and the High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 signaling pathway in Mycoplasma pneumoniae pneumonia

Fan

Ding

et al. 2021

Preprint

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Background: In recent years, reports of refractory Mycoplasma pneumoniae pneumonia (RMPP) have gradually increased, including reports on how these conditions threaten the lives of children. However, the specific mechanism of Mycoplasma pneumoniae pneumonia (MPP) remains unclear. This study aimed to investigate the relationship between community-acquired respiratory distress syndrome toxin (CARDS TX) and High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 (HMGB1-TLRs-MyD88) in MPP and to examine the immune pathogenesis of Mycoplasma pneumoniae infection. Methods: Children who were diagnosed with MPP and examined by bronchoscopy were included in the MPP group. Additionally, children who underwent bronchoscopy because of bronchial foreign bodies in the same period were included in the control group. Gene expression of CARDS TX, HMGB1, Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), MyD88, and cluster of differentiation 14 (CD14) in bronchoalveolar lavage fluid (BALF) were detected using real-time reverse transcription-polymerase chain reaction. Correlations between CARDS TX and HMGB1-TLRs-MyD88 were analyzed. Results: CARDS TX, HMGB1, TLR2, MyD88, and CD14 mRNA expression in BALF in the MPP group was significantly higher than that in the control group (all P< 0.05). CARDS TX mRNA expression was positively correlated with HMGB1, TLR2, MyD88, and CD14 mRNA expression (all P< 0.05). Furthermore, HMGB1 mRNA expression was positively correlated with TLR2, MyD88, and CD14 mRNA expression (all P< 0.05). Conclusions: CARDS TX may participate in the immune pathogenesis of MPP through the HMGB1-TLRs/CD14-MyD88 pathway.

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“…Whether these responses can control transmission of infection to the fetus without initiating preterm labor likely depends on the identity of the pathogen and the inoculum of microbe or degree of tissue damage. Highlighting their likely importance in health and disease, placentally-expressed TLRs, including those expressed specifically on syncytialized trophoblast [50] have recently been linked to the pathophysiology of preeclampsia [50,51] and early spontaneous pregnancy loss [52].…”

Section: Toll-like Receptors (Tlrs) and Stb Immune Responsesmentioning

confidence: 99%

The Immunology of Syncytialized Trophoblast

Schust

Bonney

Sugimoto

et al. 2021

IJMS

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Multinucleate syncytialized trophoblast is found in three forms in the human placenta. In the earliest stages of pregnancy, it is seen at the invasive leading edge of the implanting embryo and has been called primitive trophoblast. In later pregnancy, it is represented by the immense, multinucleated layer covering the surface of placental villi and by the trophoblast giant cells found deep within the uterine decidua and myometrium. These syncytia interact with local and/or systemic maternal immune effector cells in a fine balance that allows for invasion and persistence of allogeneic cells in a mother who must retain immunocompetence for 40 weeks of pregnancy. Maternal immune interactions with syncytialized trophoblast require tightly regulated mechanisms that may differ depending on the location of fetal cells and their invasiveness, the nature of the surrounding immune effector cells and the gestational age of the pregnancy. Some specifically reflect the unique mechanisms involved in trophoblast cell–cell fusion (aka syncytialization). Here we will review and summarize several of the mechanisms that support healthy maternal–fetal immune interactions specifically at syncytiotrophoblast interfaces.

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Toll‐like receptors signaling network in pre‐eclampsia: An updated review

Cited by 37 publications

References 98 publications

Insight Into TLR4-Mediated Immunomodulation in Normal Pregnancy and Related Disorders

Insight Into TLR4-Mediated Immunomodulation in Normal Pregnancy and Related Disorders

Investigation of the relationship between Community-acquired respiratory distress syndrome toxin and the High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 signaling pathway in Mycoplasma pneumoniae pneumonia

The Immunology of Syncytialized Trophoblast

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