|
| Status |
Public on Feb 22, 2018 |
| Title |
Human primary macrophages derived in vitro from circulating monocytes comprise adherent and non-adherent subsets with differential expression of Siglec-1 and CD4 and permissiveness to HIV-1 infection |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Macrophages are a major target for human immunodeficiency virus type 1 (HIV-1) infection. However, macrophages are largely heterogeneous and may exhibit differences in permissiveness to HIV-1 infection. This study highlights the interplay of macrophage heterogeneity in HIV-1 pathogenesis. We show that monocyte-derived macrophages (MDM) could be divided into two distinct subsets: CD14+Siglec-1hiCD4+ (non-adherent MDM), and CD14+Siglec-1LoCD4- (adherent MDM). The CD14+Siglec-1hiCD4+MDM subset represented the smaller proportion in the macrophage pool, and varied among different donors. Fractionation and subsequent exposure of the two MDM subsets to HIV-1 revealed opposite outcomes in terms of HIV-1 capture and infection. Although the CD14+Siglec-1hiCD4+MDM captured significantly more HIV-1, infection was significantly higher in the CD14+Siglec-1LoCD4-MDM subset. Thus, CD14+Siglec-1hiCD4+MDM were less permissive to infection. Depletion of CD14+Siglec-1hiCD4+MDM or a decrease in their percentage, resulted in increased infection of MDM, suggestive of a capacity of these cells to capture and sequester HIV-1 in an environment that hinders its infectivity. Increased expression of innate restriction factors and cytokine genes were observed in the non-adherent CD14+Siglec-1hiCD4+MDM, both before and after HIV-1 infection, compared to the adherent CD14+Siglec-1LoCD4-MDM. The differential expression of gene expression profiles in the two macrophage subsets may provide an explanation for the differences observed in HIV-1 infectivity.
|
| |
|
| Overall design |
Adherent and non-adherant MDM that were either uninfected or infected with HIV-1 from 3 different PBMC donors were evaluated.
|
| |
|
| Contributor(s) |
Rao M |
| Citation(s) |
29123518 |
| |
| Submission date |
Sep 08, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Mangala Rao |
| E-mail(s) |
mrao@hivresearch.org
|
| Phone |
301-319-7699
|
| Organization name |
WRAIR
|
| Street address |
503 Robert Grant Avenue
|
| City |
Silver Spring |
| State/province |
MD |
| ZIP/Postal code |
20910 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA403862 |
| SRA |
SRP117184 |
Less...
More...