Is It Time to Reconsider the Lipopolysaccharide Paradigm in Acute Graft-Versus-Host Disease?

Gautier, Thomas; Chagué, Cécile; Barros, Jean‐Paul Pais de; Deckert, Valérie; Lagrost, Laurent; Saas, Philippe

doi:10.3389/fimmu.2017.00952

Cited by 9 publications

(6 citation statements)

References 35 publications

(33 reference statements)

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“…On the colonization resistance front, genetically engineered bacteria may be used to compete with the pathogens [45]. Inducers of gut AMPs and of Toll-like receptors such as LPS [46] or pharmacological compounds [31, 47] could help reduce pathogenic microbial colonization of the gut and subsequently reduce the risk of GvHD.…”

Section: Perspectives For Therapeutic Strategies Involving the Gut MImentioning

confidence: 99%

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

et al. 2018

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The human gut microbiota gained tremendous importance in the last decade as next-generation technologies of sequencing and multiomics analyses linked the role of the microbial communities to host physiology and pathophysiology. A growing number of human pathologies and diseases are linked to the gut microbiota. One of the main mechanisms by which the microbiota influences the host is through its interactions with the host immune system. These interactions with both innate and adaptive host intestinal and extraintestinal immunity, although usually commensalistic even mutualistic with the host, in some cases lead to serious health effects. In the case of allogenic hematopoietic stem cell transplantation (allo-HSCT), the disruption of the intestinal microbiota diversity is associated with acute graft-versus-host disease (GvHD). Causing inflammation of the liver, skin, lungs, and the intestine, GvHD occurs in 40–50% of patients undergoing allo-HSCT and results in significant posttransplantation mortality. In this review, we highlight the impact of the gut microbiota on the host immunity in GvHD and the potential of microbiota in alleviation or even prevention of GvHD.

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Section: Perspectives For Therapeutic Strategies Involving the Gut MImentioning

confidence: 99%

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

et al. 2018

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“…Similarly, i.p. injection of another TLR4-ligand, lipopolysaccharide (LPS) increased abortion in rats and mice in a dose-dependent matter [ 58 , 59 ]. However, administration of different anti-inflammatory drugs protected against LPS-induced abortion.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase Protects against Placental Vascular Inflammation and Abortion by the Alarmin Heme in Mice

Suttorp

Rheden

Dijk

et al. 2020

IJMS

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Both infectious as non-infectious inflammation can cause placental dysfunction and pregnancy complications. During the first trimester of human gestation, when palatogenesis takes place, intrauterine hematoma and hemorrhage are common phenomena, causing the release of large amounts of heme, a well-known alarmin. We postulated that exposure of pregnant mice to heme during palatogenesis would initiate oxidative and inflammatory stress, leading to pathological pregnancy, increasing the incidence of palatal clefting and abortion. Both heme oxygenase isoforms (HO-1 and HO-2) break down heme, thereby generating anti-oxidative and -inflammatory products. HO may thus counteract these heme-induced injurious stresses. To test this hypothesis, we administered heme to pregnant CD1 outbred mice at Day E12 by intraperitoneal injection in increasing doses: 30, 75 or 150 μmol/kg body weight (30H, 75H or 150H) in the presence or absence of HO-activity inhibitor SnMP from Day E11. Exposure to heme resulted in a dose-dependent increase in abortion. At 75H half of the fetuses where resorbed, while at 150H all fetuses were aborted. HO-activity protected against heme-induced abortion since inhibition of HO-activity aggravated heme-induced detrimental effects. The fetuses surviving heme administration demonstrated normal palatal fusion. Immunostainings at Day E16 demonstrated higher numbers of ICAM-1 positive blood vessels, macrophages and HO-1 positive cells in placenta after administration of 75H or SnMP + 30H. Summarizing, heme acts as an endogenous “alarmin” during pregnancy in a dose-dependent fashion, while HO-activity protects against heme-induced placental vascular inflammation and abortion.

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“…In the gut, damaged epithelium and mucosa compromise the gut barrier, allowing lipopolysaccharide (LPS), an endotoxin, to leak through the mucosa into the systemic circulation. LPS binds to toll‐like receptor‐4 (TLR‐4) on innate immune cells (such as macrophages and dendritic cells) leading to the secretion of inflammatory cytokines (IL‐1β, TNF‐α, and IL‐6) 26 . These cells can establish residence in various organ tissues.…”

Section: Pathophysiology Of Gvhdmentioning

confidence: 99%

How does ocular graft‐versus‐host disease fit under the dry eye umbrella? A review

Kantor,

Tovar,

Wang

et al. 2024

Clinical Exper Ophthalmology

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Graft‐versus‐host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments.

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Is It Time to Reconsider the Lipopolysaccharide Paradigm in Acute Graft-Versus-Host Disease?

Abstract: International audienc

Cited by 9 publications

References 35 publications

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

Heme Oxygenase Protects against Placental Vascular Inflammation and Abortion by the Alarmin Heme in Mice

How does ocular graft‐versus‐host disease fit under the dry eye umbrella? A review

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