Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Kutza, Joseph; Crim, Lynne; Feldman, Steven A.; Hayes, Mark P.; Gruber, Marion F.; Beeler, Judy A.; Clouse, Kathleen A.

doi:10.4049/jimmunol.164.9.4955

Cited by 38 publications

(46 citation statements)

References 35 publications

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“…Thus, it appears that IL-32 functions as a negative regulator of HIV-1 in a feedback loop. In this study, however, we demonstrated that M-CSF, which is present at relatively high concentrations in human serum (37), is essential for the development of most tissue macrophages (11)(12)(13), and stimulates the HIV-1 replication (17)(18)(19)(20)(21), markedly counteracts the anti-HIV-1 activity of IL-32g (Figs. 3 and 4).…”

Section: Discussionmentioning

confidence: 85%

“…In contrast, M-CSF has been demonstrated to stimulate HIV-1 replication (17)(18)(19)(20)(21). Thus, we next investigated how cotreatment with M-CSF and IL-32g affects HIV-1 replication.…”

Section: Resultsmentioning

confidence: 99%

“…To infect macrophages, HIV-1 utilizes CD4 and CCR5 as its primary receptor and coreceptor, respectively. It is considered that M-CSF stimulates HIV-1 replication in macrophages, at least in part, by upregulating their cell-surface CD4 and CCR5 expression levels (17)(18)(19)(20)(21). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The essential role of the M-CSF/Fms axis in the development of most tissue macrophages has been well established using naturally occurring M-CSF-deficient op/op mice (11,12) and Fms knockout mice (13). It is also well established that M-CSF preferentially induces M2 macrophages (14)(15)(16) and stimulates HIV-1 replication in macrophages, at least in part, by upregulating the surface expression of CD4 and CCR5, which are the primary receptor and coreceptor of HIV-1, respectively (17)(18)(19)(20)(21).…”

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confidence: 99%

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M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Osman

Bhuyan

Hashimoto

et al. 2014

The Journal of Immunology

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M-CSF promotes the differentiation and survival of macrophages, and preferentially induces anti-inflammatory M2, rather than proinflammatory M1 macrophages. Recently, another cytokine, IL-32, was also shown to promote macrophage differentiation. In this article, we provide the first evidence, to our knowledge, that M-CSF has both additive and inhibitory effects on the macrophage-related activities of IL-32. When added to M-CSF–derived macrophages, M-CSF and IL-32 promoted macrophage survival, which was further enhanced by their combination. However, they had different effects on HIV-1 replication; that is, it was stimulated by M-CSF and inhibited by IL-32. Interestingly, the anti–HIV-1 activity of IL-32 was counteracted by M-CSF. Such inhibitory effect of M-CSF was not observed with IL-32–induced M1-like features including high cytokine/chemokine production and strong expression of the costimulatory molecule CD80. However, IL-32–treated macrophages unexpectedly showed also M2-like features including increased phagocytic activity, and high expression of CD14 and the scavenger receptor CD163, and the expression of CD14 and CD163 was further upregulated by cotreatment with M-CSF. The findings of this study regarding the unique functional interplay between M-CSF and IL-32 increase our understanding of the mechanisms that regulate the survival and M1/M2 ratio of macrophages, as well as HIV-1 replication in macrophages.

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Section: Discussionmentioning

confidence: 85%

“…In contrast, M-CSF has been demonstrated to stimulate HIV-1 replication (17)(18)(19)(20)(21). Thus, we next investigated how cotreatment with M-CSF and IL-32g affects HIV-1 replication.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Osman

Bhuyan

Hashimoto

et al. 2014

The Journal of Immunology

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“…14,15 Unlike monocyte-derived macrophages (MDMs), undifferentiated monocytes are not readily infected by HIV-1 in cell culture. 16,17 A productive viral infection may only occur after monocytes are differentiated after serum or cytokine stimulation, 18 a process that leads to the up-regulation of different cell-surface markers and receptors, including ␣V integrins 19,20 and, more specifically, an increase in the vitronectin ␣V␤3 receptor during the first 3 to 6 hours after infection. 14 We and others have shown the antiviral effect of specific anti-␣V antibodies in MDMs.…”

Section: Introductionmentioning

confidence: 99%

Cell adhesion through αV-containing integrins is required for efficient HIV-1 infection in macrophages

Ballana

Pauls

Senserrich

et al. 2009

Blood

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IntroductionIntegrins are a family of transmembrane cell adhesion receptors that recognize cell-surface and extracellular matrix ligands. 1 All integrins are heterodimers composed of noncovalently linked ␣ and ␤ subunits. In humans, at least 18 ␣ and 8 ␤ subunits have been identified, forming more than 20 heterodimers, each of them with different cell expression patterns and ligand specificities. 2 Integrinmediated interactions are vital to the maintenance of normal cell functioning, as they mediate the interaction between cells and with the extracellular matrix, having therefore important implications for cell adhesion, migration, and proliferation. Integrins function as mediators for cell-cell interaction and adhesion but may also elicit signal transduction events leading to cell activation and response to the extracellular stimulus. 1 Different enveloped and nonenveloped viruses use integrins to enter and replicate in host cells. 3 Integrins may act as viral receptors that mediate virus attachment to the cell, a process that may also promote signaling responses influencing viral replication at a later step. In the case of human cytomegalovirus, ␣V␤3 has been described as an entry coreceptor but also as a trigger-mediator of intracellular signaling pathways. 4 The ␣4␤7 integrin, preferentially expressed in activated T cells homing to the gut, may interact with the HIV-1 envelope glycoprotein gp120, leading to increased virus replication. 5 Human blood monocytes, originated from hematopoietic precursors in the bone marrow, give rise to mature macrophages, which are distributed ubiquitously in all tissues. 6,7 Adhesion molecules, particularly integrins, have been shown to up-regulate when monocytes differentiate into macrophages, [8][9][10] suggesting that integrins play an important role in macrophage adhesion, migration, and tissue infiltration. Blood monocytes and tissue resident macrophages are important in vivo cell targets of HIV-1 infection. [11][12][13] Macrophages may become chronically infected or serve as reservoirs of latent virus. Furthermore, HIV may sequester macrophage immunoregulatory function, that is, inducing secretion of proinflammatory cytokines that lead to recruitment and activation of new target cells for HIV, including CD4 ϩ T cells. 14,15 Unlike monocyte-derived macrophages (MDMs), undifferentiated monocytes are not readily infected by HIV-1 in cell culture. 16,17 A productive viral infection may only occur after monocytes are differentiated after serum or cytokine stimulation, 18 a process that leads to the up-regulation of different cell-surface markers and receptors, including ␣V integrins 19,20 and, more specifically, an increase in the vitronectin ␣V␤3 receptor during the first 3 to 6 hours after infection. 14 We and others have shown the antiviral effect of specific anti-␣V antibodies in MDMs. 19,20 Here, we describe the involvement of ␣V integrin-mediated adhesion in HIV-1 replication of MDMs and HeLa cells. Our data support the idea that blocking integrin ␣V interaction with it...

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GM‐CSF and M‐CSF modulate β‐chemokine and HIV‐1 expression in microglia

Cosenza

Zhao

et al. 2002

Glia

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Significant numbers of patients with acquired immunodeficiency syndrome (AIDS) develop CNS infection primarily in macrophages and microglial cells. Therefore, the regulation of human immunodeficiency virus type 1 (HIV-1) infection and activation of the brain mononuclear phagocytes subsequent to infection are important areas of investigation. In the current report, we studied the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) in the expression of antiviral beta-chemokines and HIV-1 p24 in cultures of primary human fetal microglia. We found that stimulation with GM-CSF or M-CSF induced macrophage inflammatory proteins (MIP-1alpha and MIP-1beta) and augmented RANTES expression, after HIV-1 infection of microglia. This was not due to the effect of GM-CSF on viral expression because GM-CSF was neither necessary nor stimulatory for viral infection, nor did GM-CSF enhance the expression of env-pseudotyped reporter viruses. Blocking GM-CSF-induced microglial proliferation by nocodazole had no effect on beta-chemokine or p24 expression. The functional significance of the GM-CSF-induced beta-chemokines was suggested by the finding that, in the presence of GM-CSF, exogenous beta-chemokines lost their anti-HIV-1 effects. We further show that although HIV-1-infected microglia produced M-CSF, they failed to produce GM-CSF. In vivo, GM-CSF expression was localized to activated astrocytes and some inflammatory cells in HIV-1 encephalitis, suggesting paracrine activation of microglia through GM-CSF. Our results demonstrate a complex interplay between CSFs, chemokines, and virus in microglial cells and may have bearing on the interpretation of data derived in vivo and in vitro.

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Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Cited by 38 publications

References 35 publications

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Cell adhesion through αV-containing integrins is required for efficient HIV-1 infection in macrophages

GM‐CSF and M‐CSF modulate β‐chemokine and HIV‐1 expression in microglia

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