Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
M1 and M2a polarization of human monocyte-derived macrophages inhibits HIV-1 replication by distinct mechanisms
Journal of Immunology, Volume 182, No. 10, Year 2009
Notification
URL copied to clipboard!
Description
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. Copyright © 2009 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Cassol, Edana
Italy, Milan
Irccs Ospedale San Raffaele
Italy, Milan
Università Vita-salute San Raffaele
South Africa, Pretoria
Faculty of Health Sciences
Cassetta, Luca
Italy, Milan
Irccs Ospedale San Raffaele
Italy, Milan
Università Vita-salute San Raffaele
Rizzi, Chiara
Italy, Milan
Irccs Ospedale San Raffaele
Alfano, Massimo
Italy, Milan
Irccs Ospedale San Raffaele
Poli, Guido
Italy, Milan
Irccs Ospedale San Raffaele
Italy, Milan
Università Vita-salute San Raffaele
Statistics
Citations: 194
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.4049/jimmunol.0803447
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Genetics And Genomics
Infectious Diseases