Interleukin-27-polarized HIV-resistant M2 macrophages are a novel subtype of macrophages that express distinct antiviral gene profiles in individual cells: implication for the antiviral effect via different mechanisms in the individual cell-dependent manner

被引：0

作者：

Imamichi, Tomozumi ^{[1
]}

Yang, Jun ^{[1
]}

Chen, Qian ^{[1
]}

Goswami, Suranjana ^{[1
]}

Marquez, Mayra ^{[1
]}

Kariyawasam, Udeshika ^{[1
]}

Sharma, Homa Nath ^{[1
]}

Wiscovitch-Russo, Rosana ^{[1
]}

Li, Xuan ^{[1
]}

Aioi, Akihiro ^{[2
]}

Adelsberger, Joseph W. ^{[3
]}

Chang, Weizhong ^{[1
]}

Higgins, Jeanette ^{[3
]}

Sui, Hongyan ^{[1
]}

机构：

[1] Frederick Natl Lab Canc Res, Lab Human Retrovirol & Immunoinformat, Frederick, MD 21701 USA

[2] Septem Soken, Lab Basic Res, Osaka, Japan

[3] Frederick Natl Lab Canc Res, AIDS Monitoring Lab, Frederick, MD USA

来源：

FRONTIERS IN IMMUNOLOGY | 2025年 / 16卷

基金：

美国国家卫生研究院;

关键词：

interleukin-27; M2; macrophages; polarization; anti-viral genes; scRNA seq; IMMUNODEFICIENCY-VIRUS TYPE-1; INTERFERON-INDUCIBLE GENES; ADENOSINE RECEPTORS; T-CELLS; ALTERNATIVE ACTIVATION; TRANSCRIPTION FACTOR; IL-6; EXPRESSION; REPLICATION; CYTOKINE; CALCIUM;

D O I：

10.3389/fimmu.2025.1550699

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Introduction: Interleukin (IL)-27 is an anti-viral cytokine. IL-27-treated monocyte-derived macrophages (27-Mac) suppressed HIV replication. Macrophages are generally divided into two subtypes, M1 and M2 macrophages. M2 macrophages can be polarized into M2a, M2b, M2c, and M2d by various stimuli. IL-6 and adenosine induce M2d macrophages. Since IL-27 is a member of the IL-6 family of cytokines, 27-Mac was considered M2d macrophages. In the current study, we compared biological function and gene expression profiles between 27-Mac and M2d subtypes. Methods: Monocytes derived from health donors were differentiated to M2 using macrophage colony-stimulating factor. Then, the resulting M2 was polarized into different subtypes using IL-27, IL-6, or BAY60-658 (an adenosine analog). HIV replication was monitored using a p24 antigen capture assay, and the production of reactive oxygen species (ROS) was determined using a Hydrogen Peroxide Assay. Phagocytosis assay was run using GFP-labeled opsonized E. coli. Cytokine production was detected by the IsoPlexis system, and the gene expression profiles were analyzed using single-cell RNA sequencing (scRNA-seq). Results and Discussion: 27-Mac and BAY60-658-polarized M2d (BAY-M2d) resisted HIV infection, but IL-6-polarized M2d (6-M2d) lacked the anti-viral effect. Although phagocytosis activity was comparable among the three macrophages, only 27-Mac, but neither 6-M2d nor BAY-M2d, enhanced the generation of ROS. The cytokine-producing profile of 27-Mac did not resemble that of the two subtypes. The scRNA-seq revealed that 27-Mac exhibited a different clustering pattern compared to other M2ds, and each 27-Mac expressed a distinct combination of anti-viral genes. Furthermore, 27-Mac did not express the biomarkers of M2a, M2b, and M2c. However, it significantly expressed CD38 (p<0.01) and secreted CXCL9 (p<0.001), which are biomarkers of M1. Conclusions: These data suggest that 27-Mac may be classified as either an M1-like subtype or a novel subset of M2, which resists HIV infection mediated by a different mechanism in individual cells using different anti-viral gene products. Our results provide a new insight into the function of IL-27 and macrophages.

引用

页数：23