Fibrocytes Differ from Macrophages but Can Be Infected with HIV-1

Abstract

Fibrocytes (fibroblastic leukocytes) are recently identified as unique hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes are known to contribute to the remodeling or fibrosis of various injured tissues. However, their role in viral infection is not fully understood. In this study, we show that differentiated fibrocytes are phenotypically distinguishable from macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited persistently infected cell-like phenotypes, the degree of which was more apparent than macrophages. The infected fibrocytes produced replication-competent HIV-1, but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1–induced cell death, which enabled them to support an extremely long-term HIV-1 production at low but steady levels. More importantly, our results suggested that fibrocytes were susceptible to HIV-1 regardless of their differentiation state, in contrast to the fact that monocytes become susceptible to HIV-1 after the differentiation into macrophages. Our findings indicate that fibrocytes are the previously unreported HIV-1 host cells, and they suggest the importance of considering fibrocytes as one of the long-lived persistently infected cells for curing HIV-1.

Are T cells the only HIV-1 reservoir?

“…Fibrocytes, defined as CD34+CD45+ collagen I+, have recently been reported to have characteristics of cells that can be persistently infected [104]. In vitro, infected fibrocytes resisted HIV-1 induced cell death and stably expressed low levels of HIV-1 mRNA for >60 days.…”

“…In vitro, infected fibrocytes resisted HIV-1 induced cell death and stably expressed low levels of HIV-1 mRNA for >60 days. However, there are no data on whether fibrocytes are HIV-1 infected in vivo [104]. …”

Fibrocytes, Wound Healing, and Corneal Fibrosis

“…30 Fibrocytes also express other monocyte markers such as CD11a, CD11b, CD32, and CD64, reinforcing their possible origin from monocytes. 25 It is well known that macrophages originate from monocytes, and Hashimoto et al 31 show that both macrophages and fibrocytes express Hck and Lyn-Src family kinases-the expression of which is often cell lineage specific.…”

Expression of IL‐34 correlates with macrophage infiltration and prognosis of diffuse large B‐cell lymphoma

“…49 In brief, TF-1-fms cells maintained with M-CSF were M-CSFdepleted for 6 h, and then either left untreated or treated with IL-34 or M-CSF for various periods at 37°C. 49 In brief, TF-1-fms cells maintained with M-CSF were M-CSFdepleted for 6 h, and then either left untreated or treated with IL-34 or M-CSF for various periods at 37°C.…”

“…The expression of CSF1R on the surface of TF-1fms cells was detected by flow cytometry on a FACSVerse (BD Biosciences) using FlowJo software (Tree Star) as described previously. 49 In brief, TF-1-fms cells maintained with M-CSF were M-CSFdepleted for 6 h, and then either left untreated or treated with IL-34 or M-CSF for various periods at 37°C. Ice-cold PBS was added to the cell suspensions, and then, the cells were analysed for CSF1R expression using PE-labelled anti-CSF1R antibody (clone 3-4A4-E4; Santa Cruz Biotechnology).…”