Macrophage activation and human immunodeficiency virus infection: HIV replication directs macrophages towards a pro-inflammatory phenotype while previous activation modulates macrophage susceptibility to infection and viral production.
Macrophages are pivotal for the regulation of immune and inflammatory responses, but whether their role in HIV infection is protective or deleterious remains unclear. In this study, we investigated the effect of pro- and anti-inflammatory stimuli on macrophage sensitivity to two different aspects of HIV infection: their susceptibility to infection stricto sensu, which we measured by endpoint titration method, and their ability to support virus spread, which we measured by using an RT activity assay in infection kinetics. We show a partially protective role for pro-inflammatory agents as well as for IL-4. We also illustrate that various different stimuli display differential effects on macrophage susceptibility to HIV and on virus replication that occurs thereafter. On the other hand, HIV replication strongly repressed CD206 and CD163 expression, thus clearly orientating macrophages towards a pro-inflammatory phenotype, but independently of TNF. Taken together, our results emphasize that HIV infection of macrophages sets up inflammation at the cell level but through unexpected mechanisms. This may limit target susceptibility and participate in virus clearance but may also result in tissue damage.
Laboratoire de Neuro-Immuno-Virologie, Service de Neurovirologie, UMR E-01 CEA, Université Paris-Sud, DSV/DRM, Centre de Recherches du Service de Santé des Armées, IPSC, Fontenay aux Roses, France.
Fabrice
F
Porcheray
Boubekeur
B
Samah
Cathie
C
Léone
Nathalie
N
Dereuddre-Bosquet
Gabriel
G
Gras
D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D015704:CD4 Antigens / Q000032:analysis; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D054303:HIV Reverse Transcriptase / Q000032:analysis; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000821:virology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D014779:Virus Replication; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D015704:CD4 Antigens; D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D054303:HIV Reverse Transcriptase