Endogenous CCL2 (monocyte chemotactic protein-1) modulates human immunodeficiency virus type-1 replication and affects cytoskeleton organization in human monocyte–derived macrophages

Fantuzzi, Laura; Spadaro, Francesca; Vallanti, Giuliana; Canini, Irene; Ramoni, Carlo; Vicenzi, Elisa; Belardelli, Filippo; Poli, Guido; Gessani, Sandra

doi:10.1182/blood-2002-10-3275

Cited by 57 publications

(58 citation statements)

References 29 publications

(22 reference statements)

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“…CCL2 is involved in the early recruitment of monocytes to inflammatory lesions (14) and has been shown to enhance the replication of X4 HIV-1 strains in activated PBMC (54). Neutralization of this chemokine has been shown to inhibit the late phase of virion release in primary MDM (74). Thus, the reduction in CCL2 secretion may have contributed to the prolonged postentry inhibition of HIV-1 replication observed in M2a but not in M1 MDM.…”

Section: Discussionmentioning

confidence: 99%

M1 and M2a Polarization of Human Monocyte-Derived Macrophages Inhibits HIV-1 Replication by Distinct Mechanisms

Cassol

Cassetta

Rizzi

et al. 2009

The Journal of Immunology

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The capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines and other extracellular stimuli. In this study, we demonstrate that cytokine-induced polarization of human monocyte-derived macrophage (MDM) into either classical (M1) or alternatively activated (M2a) MDM is associated with a reduced capacity to support productive CCR5-dependent (R5) HIV-1 infection. M1 polarization was associated with a significant down-regulation of CD4 receptors, increased secretion of CCR5-binding chemokines (CCL3, CCL4, and CCL5), and a >90% decrease in HIV-1 DNA levels 48-h postinfection, suggesting that the inhibition occurred at an early preintegration step in the viral life cycle. In contrast, M2a polarization had no effect on either HIV-1 DNA or protein expression levels, indicating that inhibition occurred at a late/postintegration level in the viral life cycle. M2a inhibition was sustained for up to 72-h postinfection, whereas M1-effects were more short-lived. Most phenotypic and functional changes were fully reversible 7 days after removal of the polarizing stimulus, and a reciprocal down-regulation of M1-related chemokines and cytokines was observed in M2a MDM and vice versa. Since reversion to a nonpolarized MDM state was associated with a renewed capacity to support HIV replication to control levels, M1/M2a polarization may represent a mechanism that allows macrophages to cycle between latent and productive HIV-1 infection.

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Section: Discussionmentioning

confidence: 99%

M1 and M2a Polarization of Human Monocyte-Derived Macrophages Inhibits HIV-1 Replication by Distinct Mechanisms

Cassol

Cassetta

Rizzi

et al. 2009

The Journal of Immunology

Self Cite

175

203

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“…32 Similarly, it has also been shown that endogenous MCP-1 could modulate HIV-1 replication and might act as an enhancing factor for HIV-1 spreading in monocyte-derived macrophages. 33 This is the first report showing that pneumonia complications of SHIV infection in macaques, irrespective of the proliferating opportunistic pathogen, are associated with enhanced replication of the lentivirus in the lung.…”

Section: Discussionmentioning

confidence: 99%

Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Sui

Pinson

et al. 2005

The American Journal of Pathology

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“…Thus, HIV-1 gp120-mediated PC-PLC activation in MDMs is critical for the regulation of CCL2 secretion, a CC-chemokine playing a regulatory role in HIV infection of these cells. 37 This finding suggests that this signal transduction pathway can also be relevant for the modulation of viral replication in MDMs as well as for the recruitment of new cell targets. Overall, the identification of PC-PLC as a novel signal transduction pathway mediating some of the gp120 biologic effects unravels a new mechanism by which HIV-1 may deregulate macrophage functions and contribute to AIDS pathogenesis.…”

Section: Introductionmentioning

confidence: 97%

Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB–driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages

Fantuzzi

Spadaro

Purificato

et al. 2008

Blood

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CCL2 (MCP-1) has been shown to enhance HIV-1 replication. The expression of this chemokine by macrophages is up-modulated as a consequence of viral infection or gp120 exposure. In this study, we show for the first time that the phosphatidylcholinespecific phospholipase C (PC-PLC) is required for the production of CCL2 triggered by gp120 in human monocyte-derived macrophages (MDMs). Using a combination of pharmacologic inhibition, confocal laserscanner microscopy, and enzymatic activity assay, we demonstrate that R5 gp120 interaction with CCR5 activates PC-PLC, as assessed by a time-dependent modification of its subcellular distribution and a concentration-dependent increase of its enzymatic activity. Furthermore, PC-PLC is required for NF-kB-mediated CCL2 production triggered by R5 gp120. Notably, PC-PLC activation through CCR5 is specifically induced by gp120, since triggering CCR5 through its natural ligand CCL4 (MIP-1␤) does not affect PC-PLC cellular distribution and enzymatic activity, as well as CCL2 secretion, thus suggesting that different signaling pathways can be activated through CCR5 interaction with HIV-1 or chemokine ligands. The identification of PC-PLC as a critical mediator of well-defined gp120-mediated effects in MDMs unravels a novel mechanism involved in bystander activation and may contribute to define potential therapeutic targets to block Env-triggered pathologic responses. (Blood. 2008;111:3355-3363)

show abstract

Endogenous CCL2 (monocyte chemotactic protein-1) modulates human immunodeficiency virus type-1 replication and affects cytoskeleton organization in human monocyte–derived macrophages

Cited by 57 publications

References 29 publications

M1 and M2a Polarization of Human Monocyte-Derived Macrophages Inhibits HIV-1 Replication by Distinct Mechanisms

M1 and M2a Polarization of Human Monocyte-Derived Macrophages Inhibits HIV-1 Replication by Distinct Mechanisms

Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques

Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB–driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages

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