Dynamics of human monocytes and airway macrophages during healthy aging and after transplant

Abstract

The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant. We characterized monocyte/macrophage populations from the peripheral blood and airways of healthy volunteers across infancy/childhood (2–12 yr), maturity (20–50 yr), and older adulthood (>50 yr). Single-cell RNA sequencing (scRNA-seq) was performed on airway inflammatory cells isolated from sex-mismatched lung transplant recipients. During healthy aging, the proportions of blood and bronchoalveolar lavage (BAL) classical monocytes peak in adulthood and decline in older adults. scRNA-seq of BAL cells from lung transplant recipients indicates that after transplant, the majority of AMs are recipient derived. These data show that during aging, the peripheral monocyte phenotype is consistent with that found in the airways and, furthermore, that the majority of human AMs after transplant are derived from circulating monocytes.

Characterization of the Bronchoalveolar Lavage Fluid by Single Cell Gene Expression Analysis in Healthy Dogs: A Promising Technique

“…Four subpopulations of macrophages/monocytes were found. Among them, 3 subpopulations corresponded to AMs based on their expression of MARCO (25,27). AMs are the most abundant cells found in the airways in homeostatic conditions.…”

“…In each cluster, a selection of the most overexpressed transcripts able to differentiate cell types according to the literature is displayed in Table 3. Cells of clusters 0, 3, 5, and 8 expressing MARCO and/or MSR1 and/or HLA-DRB1 and/or CD163 and/or CD86 and/or MRC1 and/or CD68 and/or CD63 were identified as macrophages/monocytes (25)(26)(27)(28)(29)(30)(31)(32). Cells of cluster 1 and 2 expressing CD3 markers were identified as T lymphocytes (28,33).…”

“…The graph-based clustering of merged single-cells identified four transcriptionally distinct clusters of macrophages/monocytes. In this study, MARCO, a class A scavenger receptor involved in host defense and demonstrated to be highly expressed in embryonic-derived or alveolar macrophages (AMs) and not expressed in monocyte-derived macrophages was used to identify AMs (25,27). MARCO was overexpressed in the clusters 0, 3, and 5 compared to all remaining clusters (Figure 2 and Supplementary Table 3).…”

Immune responses during COVID-19 infection

“…40 The human AM population was therefore assumed to be much more dynamic and unstable than that observed in mice. 40 Pulmonary macrophages, more specifically AMs, can control lung-resident memory T cells (TRMs). 41 TRMs are perfectly positioned to mediate rapid protection against respiratory pathogens such as coronavirus.…”

Cell Cycle Regulation in Macrophages and Susceptibility to HIV-1

“…Nevertheless, recent transplantation studies have provided some new views and have shown that donor-derived macrophages persist for many years in transplanted skin or liver in patients [29]. Furthermore, lung macrophages can self-renew for years in a murine model [30,31], but recent work on alveolar macrophage ontogeny in the human lung during healthy aging and after transplant suggests that donor alveolar macrophages are quickly replaced from the recipient peripheral circulating monocytes [32]. Interestingly, the human myocardium contains two distinct subsets of macrophages: CCR2− and CCR2+ (C-C chemokine receptor type 2).…”