Intestinal Microbiota Influence Immune Tolerance Post Allogeneic Hematopoietic Cell Transplantation and Intestinal GVHD.

Natalie Köhler,Robert Zeiser

doi:10.3389/fimmu.2018.03179

Natalie Köhler, Robert Zeiser

Open Access

https://doi.org/10.3389/fimmu.2018.03179

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Abstract

Under normal conditions our intestines are inhabited by trillions of diverse microorganisms composing the intestinal microbiota, which are mostly non-pathogenic anaerobic commensal bacteria vital for the maintenance of immune homeostasis. The composition and diversity of the intestinal microbiota can be disturbed by various factors including diet, antibiotics, and exposure to intestinal pathogens. Alterations of the intestinal microbiota contributes to many diseases including graft-vs.-host disease (GVHD), a life threatening complication that occurs after allogeneic hematopoietic cell transplantation (allo-HCT) caused by an allogeneic reaction of donor T cells against recipient target tissues. Intestinal GVHD is most difficult to treat and connected to a high mortality. Due to recent advances in high-throughput sequencing technology, composition of the microbiome during allo-HCT has been characterized, and some common patterns have been identified. Metabolites produced by intestinal bacteria were shown to promote intestinal tissue homeostasis and immune tolerance post-allo-HCT. In this review, we discuss the role of the intestinal microbiota and metabolites in the context of acute GVHD. Moreover, novel therapeutic approaches that aim at protecting or regenerating intestinal cell populations will be highlighted.

Highlights

Allogeneic hematopoietic cell transplantation is the only curative therapy option for most acute leukemias
In addition to the hematopoietic stem cells (HSCs), the graft contains allogeneic donor T cells, which can on the one hand attack residual malignant cells, known as graft-vs.-leukemia (GvL) effect, but on the other hand may attack healthy host tissues, resulting in graft-vs.-host disease (GVHD)
While previous reports have already demonstrated a critical role of NLRP3 inflammasome activation in host APCs for the full manifestation of GVHD [63], this study shows that it has the opposite effect in non-hematopoietic

Summary

Introduction

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative therapy option for most acute leukemias. The important influence of intestinal microbiota on immune responses, including post-allo-HCT, becomes more and more recognized and the gut is one of the main targets of acute GVHD. The first hint that the intestinal microbiota affect GVHD development dates back to the early 1970s, when first studies in murine models showed that GVHD was reduced and survival was prolonged in antibiotics-treated or germ-free mice undergoing allo-HCT [11,12,13].

Results

Conclusion