Cytokine Cocktail Promotes Alveolar Macrophage Reconstitution and Functional Maturation in a Murine Model of Haploidentical Bone Marrow Transplantation.

Hong Cheng ,Ming Chen,Hongyun Lu,Rong Jin,Xiaoqiu Dai,Hongmin Wang,Xiaohong Huang,Fang‐Yuan Gong ,Han Dong ,Xiao‐Ming Gao

doi:10.3389/fimmu.2021.719727

Abstract

Infectious pneumonia is one of the most common complications after bone marrow transplantation (BMT), which is considered to be associated with poor reconstitution and functional maturation of alveolar macrophages (AMs) post-transplantation. Here, we present evidence showing that lack of IL-13-secreting group 2 innate lymphoid cells (ILC2s) in the lungs may underlay poor AM reconstitution in a mouse model of haploidentical BMT (haplo-BMT). Recombinant murine IL-13 was able to potentiate monocyte-derived AM differentiation in vitro. When intranasally administered, a cocktail of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and CCL2 not only promoted donor monocyte-derived AM reconstitution in haplo-BMT-recipient mice but also enhanced the innate immunity of the recipient animals against pulmonary bacterial infection. These results provide a useful clue for a clinical strategy to prevent pulmonary bacterial infection at the early stage of recipients post-BMT.

Highlights

Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective strategies to treat multiple diseases and disorders related with hematopoiesis failure, as well as blood malignancies
By using a mouse model of haplo-bone marrow transplantation (BMT), we demonstrate that lung group 2 innate lymphoid cell (ILC2)-derived IL-13 is critical for monocyte–alveolar macrophages (AMs) differentiation after BMT and that IL-13-based cytokine cocktail could effectively promote AM reconstitution post-BMT, thereby enhancing innate immunity against respiratory bacterial infection
Our data show that administration of recombinant IL13, together with recombinant CCL2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), could effectively promote donor-derived AM reconstitution in vivo and enhance the resistance of TCD-BMT recipients against respiratory bacterial infection (Figure 6)

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective strategies to treat multiple diseases and disorders related with hematopoiesis failure, as well as blood malignancies. Infectious complications are major cause of increased morbidity and mortality in HSCT recipients, which involve bacterial, viral, and fungal infections in different organs and tissues [1]. The development of effective treatment for infectious complications after HSCT is still challenging due to our poor. Whether donor stem cell rapidly and effectively engrafts and reconstitutes innate immune system is essential to protect HSCT recipients against challenging of respiratory pathogens. HSCT recipients beyond the period of neutropenia are vulnerable to bacterial infection, which often sustain to the late post-engraftment period, indicating a long-term immune dysfunction of donor-derived innate immune system [7, 8]

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Results

Conclusion