Neutrophils recognize and amplify IFNT signals derived from day 7 bovine embryo for stimulation of ISGs expression in vitro: A possible implication for the early maternal recognition of pregnancy

Fiorenza, M. F.; Marey, Mohamed Ali; Rashid, Mohammad Bazlur; Zinnah, Mohammad Ali; Ma, Dongxue; Morillo, Vernadyn; Kusama, Kaoru; Shimada, M.; Imakawa, Kazuhiko; Antoniazzi, Alfredo Q.; Miyamoto, Akio

doi:10.1016/j.bbrc.2021.03.037

Cited by 10 publications

(6 citation statements)

References 28 publications

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“…Therefore, we suggest that the IFNT induces Apo‐A1 release to amplify the embryo signal and initiate more anti‐inflammatory conditions throughout the entire endometrial milieu. In the same line, recently we reported that neutrophils can amplify and transfer embryo‐derived IFNT signals to a new cell population in a cell‐to‐cell communication mechanism possibly mediated in part by interferon‐alpha 65 . It seems that the pre‐hatching bovine embryo releases minute amounts of IFNT, which triggers anti‐inflammatory responses either directly at the very local embryo‐maternal interface or through the induction of the release of specific molecules from the endometrial mucosa which amplify and generalize such Th2 signals throughout the entire uterine milieu for embryo tolerance.…”

Section: Discussionmentioning

confidence: 84%

Intrauterine infusion of low levels of interferon‐tau on day‐8 post‐estrus stimulates the bovine endometrium to secrete apolipoprotein‐A1: A possible implication for early embryo tolerance

Rashid

Marey

Fukuda

et al. 2022

American J Rep Immunol

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We previously reported that interferon-tau (IFNT), derived from day-7 blastocyst, generates anti-inflammatory responses in bovine endometrial epithelial cells (BEECs) in vitro. However, the real in vivo impact of early embryo-derived IFNT on the uterine proteomic profile is mostly unknown. This study aimed to investigate proteomic changes of uterine flush (UF) when infused with a low physiological level of IFNT without embryo on day-8 post-estrus and its possible impact on the uterine immunological microenvironment. First, a fresh medium was infused into the uterine lumen on day-6, from which UF was obtained 24 h later, and this procedure was repeated on day-7 (control UF). On day-8, this procedure was done with a medium containing recombinant bovine IFNT (100 pg/ml) (IFNT-supplemented UF). Control and IFNTsupplemented UF were tested for immune responses in peripheral blood mononuclear cells (PBMCs). Real-time PCR results revealed that IFNT-supplemented UF downregulated pro-inflammatory cytokines (TNFA, IL1B) and upregulated anti-inflammatory cytokine (TGFB1) and PTGES in PBMCs. Through 2-D PAGE, followed by TOF/TOF mass spectrometer, apolipoprotein-A1 (Apo-A1) protein was identified in the IFNTsupplemented UF, which was confirmed by ELISA analysis. Proteomic analysis revealed again that the in vitro stimulation of BEECs by IFNT upregulated Apo-A1 expression.Further, stimulation of PBMCs with recombinant bovine Apo-A1 downregulated TNFA and NFKB and upregulated TGFB1 and PTGES in PBMCs. Altogether, our results suggest that minute amounts of IFNT alone, normally secreted from bovine blastocyst, stimulate Apo-A1 secretion from the endometrial epithelium in the absence of embryo that initiates an anti-inflammatory environment, which could pave the way for the acceptance of early embryo in the uterus.

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Section: Discussionmentioning

confidence: 84%

Intrauterine infusion of low levels of interferon‐tau on day‐8 post‐estrus stimulates the bovine endometrium to secrete apolipoprotein‐A1: A possible implication for early embryo tolerance

Rashid

Marey

Fukuda

et al. 2022

American J Rep Immunol

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“…The differences in cytokine levels in the supernatant of CD146+/-MSCs exposed to LPS might be the reason for this difference. CD146 + MSCs secreted increased levels of IL15 and IFNγ, which are related to the promotion of antigen presentation, antibody production and improvements in macrophage lysosomal activity [40,41]. In addition, the higher levels of IL10 and VEGF in the CD146 + group achieved a better effect on antiin ammation and regeneration.…”

Section: Discussionmentioning

confidence: 97%

CD146+ umbilical cord mesenchymal stem cells exhibit higher immunomodulatory activity and therapeutic efficacy in septic mice

Zhang

Liu

et al. 2022

Preprint

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Background Several animal studies have shown that MSCs can significantly improve the survival of sepsis. CD146 + MSCs, a subpopulation of mesenchymal stem cell (MSCs), correlate with high therapeutic and secretory potency. However, their therapeutic effect on sepsis and detail mechanisms about regulation of macrophage have not been explored. Methods The effect of CD146+/-MSCs on differentiation of Treg,Th1,Th17 subsets was evaluated by flow cytometry. The paracrine effects of CD146+/-MSCs on RAW264.7 phagocytosis and LPS-stimulated polarization were studied using a co-culture protocol. In addition, we employed Luminex bead array and RNA sequencing analysis to determine the mechanisms of MSCs on LPS-stimulated RAW264.7. The Arg1 protein was detected by Western blot. CD146+/-MSCs were injected into LPS-induced sepsis mice by tail vein. The treatment effect was assessed by organ HE staining, T-cell subsets, cytokine in plasma, peritoneal macrophages, infiltrating monocytes subpopulations. Results In vitro, CD146 + MSCs could significantly increase the Treg cells proportion in PBMCs stimulated by PHA. Both CD146+/-MSCs can reduce the proportion of Th1 and Th17 subsets. CD146 + MSCs can increase the phagocytic rate of raw264.7. The RNA sequencing data indicated that UC-MSCs therapy improved LPS-induced raw264.7 through PPAR and cytokine receptor pathways. The differences between the CD146 + and CD146- groups were clustered in arginine metabolism. CD146 + MSCs decreased NO production and increased agr1 expression. CD146 + MSCs secreted higher IL15,IFNγ, VEGF and lower IL1β, IL8 under LPS. In vivo, CD146+/-MSCs treatment can improve the pathological damage of organs caused by LPS. CD146+/-MSCs therapy significantly decreased CD4 expression, increased CD8 expression, and decreased CD4/CD8 ratios, which was similar to that in the normal group. CD146+/-MSCs can reduce IL1β,IL6 content in plasma. The level of IL10 at 24h and CXCL1 at 12h in CD146 + MSCs group was the highest. The phagocytic capacity of peritoneal macrophages in CD146 + MSCs group was better than that in CD146- group and LPS group at 12h. The CD146+/-MSCs had significantly reduced numbers of monocytes in the peritoneal cavity. CD146 + MSCs enhanced the ratios of CD11b + Ly6Clo reparative monocytes and CD11b + Ly6Chi inflammatory monocytes until 24h. Conclusions Compared with CD146-MSCs, CD146 + MSCs can accelerates the end of the inflammatory response and have robust anti-inflammatory effects, by increasing the Treg cells, promoting macrophage phagocytosis, enhancing the reparative macrophage, secreting more VEGF, etc.

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“…In pregnant cows, PMNs showed an anti-inflammatory response with greater expression of TGFB, IL10, and forkhead box P3 (FOXP3) (Talukder et al, 2019). Pro-inflammatory cytokines data have shown biases in different studies; however, expression patterns seem to increase according to the development of pregnancy (Figure 1) (Fiorenza et al, 2021;Manjari et al, 2016;Sheikh et al, 2019;Shirasuna et al, 2012). Depending on their activation status, neutrophils can regulate other innate and adaptative immune cell activities and functions (Pillay et al, 2012) and IFNG production (Costantini and Cassatella, 2011).…”

Section: Maternal Recognition Of Pregnancy and Neutrophilsmentioning

confidence: 99%

“…TGFB and granulocyte colony-stimulating factor (GCSF) modulate polarization to an antiinflammatory phenotype (Casbon et al, 2015;Fridlender et al, 2009;Waight et al, 2011), while IFNB acts as a regulator of the pro-inflammatory phenotype (Jablonska et al, 2010;Wu et al, 2015). Stimulation of cows' PMNs with IFNT in vitro generated an antiinflammatory response by expressing ISGs and TGFB, CD16, and ARG1 (Fiorenza et al, 2021), well-known markers to maternal immune response suppression (Kropf et al, 2007).…”

Section: Maternal Recognition Of Pregnancy and Neutrophilsmentioning

confidence: 99%

“…In an in vitro experiment, PMNs were primed, washed to remove IFNT, and then re-incubated to comprehend if, even after removing IFNT from the system, PMNs could secrete different molecules to continue amplifying the IFNT signal to a different set of PMNs. As a result, PMNs had an IFN-like response with upregulation of ISGs and signal transducer and activator of transcription 1 (STAT1), implying that PMNs produce more IFNs, particularly IFNA, to amplify the IFNT signal around Day 7 (Figure 2) and create a tolerant environment during early pregnancy (Fiorenza et al, 2021). Therefore, neutrophils significantly impact because of their ability to act as first responder cells even during pregnancy, transfer signals to other cells locally or systemically, and regulate their functions as a result.…”

Section: Maternal Recognition Of Pregnancy and Neutrophilsmentioning

confidence: 99%

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Possible impact of neutrophils on immune responses during early pregnancy in ruminants

et al. 2021

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The interaction between early embryo and maternal immune system for the establishment of pregnancy is the focus of several studies; however, it remains unclear. The maternal immune response needs to keep a balance between avoiding any damage to the conceptus and maintaining its function in combating microbes as well. When conceptus-maternal crosstalk cannot achieve this balance, pregnancy losses might occur. Intercommunication between mother and conceptus is fundamental during early pregnancy to dictate the outcome of pregnancy. In ruminants, the embryo reacts with the maternal system mainly via interferon tau (IFNT) release. IFNT can act locally on the embryo and endometrial cells and systemically in several tissues and cells to regulate their response via the expression of interferon-stimulated genes (ISGs). Also, IFNT can induce the expression of inflammatory-related genes in immune cells. Day 7 embryo induces a shift in the maternal immune response towards anti-inflammatory (Th2) immune responses. During maternal recognition of pregnancy, peripheral mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) express markers that configure an anti-inflammatory response. However, PMNs response is more sensitive to the effects of IFNT. PMNs are more likely to express interferon-stimulated genes (ISGs), transforming growth factor-beta (TGFB), interleukin 10 (IL10), and arginase-1 (ARG1), configuring one of the most rapid immune responses to early pregnancy. This review focus on the local and peripheral immune responses during early pregnancy in ruminants, mainly the PMNs function in the immune system.

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Neutrophils recognize and amplify IFNT signals derived from day 7 bovine embryo for stimulation of ISGs expression in vitro: A possible implication for the early maternal recognition of pregnancy

Cited by 10 publications

References 28 publications

Intrauterine infusion of low levels of interferon‐tau on day‐8 post‐estrus stimulates the bovine endometrium to secrete apolipoprotein‐A1: A possible implication for early embryo tolerance

Intrauterine infusion of low levels of interferon‐tau on day‐8 post‐estrus stimulates the bovine endometrium to secrete apolipoprotein‐A1: A possible implication for early embryo tolerance

CD146+ umbilical cord mesenchymal stem cells exhibit higher immunomodulatory activity and therapeutic efficacy in septic mice

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

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