Broad-Spectrum Antibiotics Deplete Bone Marrow Regulatory T Cells.

Hyojeong Han,Hannah Yan,Katherine Y King

doi:10.3390/cells10020277

Abstract

Bone marrow suppression, including neutropenia, is a major adverse effect of prolonged antibiotic use that impairs the clinical care and outcomes of patients with serious infections. The mechanisms underlying antibiotic-mediated bone marrow suppression remain poorly understood, with initial evidence indicating that depletion of the intestinal microbiota is an important factor. Based on our earlier studies of blood and bone marrow changes in a mouse model of prolonged antibiotic administration, we studied whether changes in megakaryocytes or regulatory T cells (Tregs), two cell types that are critical in the maintenance of hematopoietic stem cells, contribute to antibiotic-mediated bone marrow suppression. Despite increased platelet numbers, megakaryocytes were unchanged in the bone marrow of antibiotic-treated mice; however, Tregs were found to be significantly depleted. Exogenous addition of Tregs was insufficient to rescue the function of bone marrow from antibiotic-treated mice in both colony formation and transplantation assays. These findings indicate that the intestinal microbiota support normal Treg development to protect healthy hematopoiesis, but that the restoration of Tregs alone is insufficient to restore normal bone marrow function.

Highlights

Received: 23 November 2020Antibiotic therapy is necessary to treat life-threatening bacterial infections, with approximately 249.8 million antibiotic prescriptions being issued in the United States annually [1]
We performed flow cytometric analysis of bone marrow to identify differentiated cell populations (Supplementary Figure S1). These analyses revealed that antibiotic-treated mice demonstrated decreased neutrophil count, CD4:CD8 ratio and bone marrow cellularity (Figure 1E–H) compared to the control mice
We investigated two aspects of the bone marrow microenvironment that could contribute to antibiotic-associated bone marrow suppression [8]

Summary

Introduction

Antibiotic therapy is necessary to treat life-threatening bacterial infections, with approximately 249.8 million antibiotic prescriptions being issued in the United States annually [1]. Prolonged use of antibiotics (two weeks or longer) is associated with adverse events, including bone marrow suppression [2,3,4,5]. With incidence ranging between 5–34%, bone marrow suppression is one of the most common antibiotic-associated adverse events, and can present as anemia and/or neutropenia [6]. Antibiotic-associated bone marrow suppression leads to unplanned outpatient visits, hospitalizations and early discontinuation of antibiotic therapy [3]. Survival for some, immunocompromised oncology and bone marrow transplant patients, may depend on continuing antibiotic therapy, precluding early discontinuation. Despite the magnitude of this problem, the mechanisms underlying antibiotic-associated bone marrow suppression remain poorly understood

Methods

Results

Conclusion