scholarly journals Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 671-674 ◽  
Author(s):  
Xu Wang ◽  
Li Ye ◽  
Wei Hou ◽  
Yu Zhou ◽  
Yan-Jian Wang ◽  
...  

AbstractAlthough both monocytes and macrophages possess essential requirements for HIV-1 entry, peripheral blood monocytes are infrequently infected with HIV-1 in vivo and in vitro. In contrast, tissue macrophages and monocyte-derived macrophages in vitro are highly susceptible to infection with HIV-1 R5 tropic strains. We investigated intracellular anti–HIV-1 factors that contribute to differential susceptibility of monocytes/macrophages to HIV-1 infection. Freshly isolated monocytes from peripheral blood had significantly higher levels of the anti–HIV-1 microRNAs (miRNA, miRNA-28, miRNA-150, miRNA-223, and miRNA-382) than monocyte-derived macrophages. The suppression of these anti–HIV-1 miRNAs in monocytes facilitates HIV-1 infectivity, whereas increase of the anti–HIV-1 miRNA expression in macrophages inhibited HIV-1 replication. These findings provide compelling and direct evidence at the molecular level to support the notion that intracellular anti–HIV-1 miRNA-mediated innate immunity may have a key role in protecting monocytes/macrophages from HIV-1 infection.

AIDS ◽  
2001 ◽  
Vol 15 (8) ◽  
pp. 945-955 ◽  
Author(s):  
Katherine Kedzierska ◽  
Johnson Mak ◽  
Anthony Jaworowski ◽  
Alison Greenway ◽  
Antoniette Violo ◽  
...  

Author(s):  
Dan Smelter ◽  
Mary Hayney ◽  
George Sakoulas ◽  
Warren Rose

Cefazolin and ertapenem has been shown to be an effective salvage regimen for refractory methicillin-susceptible Staphylococcus aureus bacteremia. Our findings suggest cefazolin plus ertapenem in vitro stimulates interleukin-1β release from peripheral blood monocytes both with and without S. aureus presence. This IL-1β augmentation was primarily driven by ertapenem. These findings support further exploration of cefazolin plus ertapenem in MSSA bacteremia and may partially explain its marked potency in vivo despite modest synergy in vitro .


1988 ◽  
Vol 168 (3) ◽  
pp. 1111-1125 ◽  
Author(s):  
C F Perno ◽  
R Yarchoan ◽  
D A Cooney ◽  
N R Hartman ◽  
S Gartner ◽  
...  

Because of the probable role of HIV-infected monocyte/macrophages in the pathogenesis and progression of AIDS, it is essential that antiretroviral therapy address viral replication in cells of this lineage. Several dideoxynucleosides have been shown to have potent in vitro and, in the case of 3'-azido-2',3'-dideoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC), in vivo activity against HIV. However, because these compounds must be phosphorylated (activated) in target cells, and because monocyte/macrophages may have levels of kinases that differ from those in lymphocytes, we investigated the capacity of these drugs to suppress HIV replication in monocyte/macrophages using HIV-1/HTLV-IIIBa-L (a monocytotropic isolate). In the present study, we observed that HTLV-IIIBa-L replication in fresh human peripheral blood monocyte/macrophages was suppressed by each of three dideoxynucleosides: 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyadenosine (ddA). Similar results were observed in 5-d-cultured monocyte/macrophages, although higher concentrations of the drugs were required. We then studied the metabolism of AZT and ddC in such cells. The phosphorylation of ddC to a triphosphate moiety was somewhat decreased in monocyte/macrophages as compared with H9 T cells. On the other hand, the phosphorylation of AZT in monocyte/macrophages was markedly decreased to 25% or less of the level in T cells. However, when we examined the level of the normal endogenous 2'-deoxynucleoside triphosphate pools, which compete with 2',3'-dideoxynucleoside triphosphate for viral reverse transcriptase, we found that the level of 2'-deoxycytidine-triphosphate (dCTP) was six- to eightfold reduced, and that of 2'-deoxythymidine-triphosphate (dTTP) was only a small fraction of that found in T cell lines. These results suggest that the ratio of dideoxynucleoside triphosphate to normal deoxynucleoside triphosphate is a crucial factor in determining the antiviral activity of dideoxynucleosides in HIV target cells, and that the lower levels of dTTP may account for the antiretroviral activity of AZT in the face of inefficient phosphorylation of this compound.


2005 ◽  
Vol 12 (10) ◽  
pp. 1202-1208 ◽  
Author(s):  
Giulia Freer ◽  
Donatella Matteucci ◽  
Paola Mazzetti ◽  
Leonia Bozzacco ◽  
Mauro Bendinelli

ABSTRACT Dendritic cells (DCs) are professional antigen-presenting cells that can prime T cells and polarize the cellular immune response. Because Th1-type immune responses have been connected to success in combating viral infection, a promising therapeutic application of DCs would be their differentiation in vitro and injection back into the host to boost an immune response in infected animals. This study was aimed both at developing a protocol to cultivate feline DCs in the absence of exogenous proteins for their use in vivo and at investigating what might be the most appropriate stimulus to induce their maturation in vitro and finding correlates of maturation. We generated DCs from peripheral blood monocytes in the presence of feline interleukin-4 and granulocyte-macrophage colony stimulating factor, and after 5 days their maturation was induced with either lipopolysaccharide, human recombinant tumor necrosis factor alpha, poly(I:C), or activated feline platelets. After 48 h, their CD14, CD1a, major histocompatibility complex class II, and B7.1 surface expression was analyzed in parallel with their ability to uptake antigen or prime a mixed leukocyte reaction. The results presented show that feline DCs cultured in autologous plasma differentiate and are able to mature in the presence of stimuli similar to the ones currently used for other species. The present work sets the grounds for future use of DCs obtained by the protocol described for in vivo vaccination and immunotherapy of feline immunodeficiency virus-infected cats.


Author(s):  
Melappa Govindappa ◽  
V. Thanuja ◽  
S. Tejashree ◽  
C.A. Soukhya ◽  
Suresh Barge ◽  
...  

The present work was aimed to identify phytochemicals in C. uredinicola methanol extract from qualitative, TLC and GC-MS method and evaluated for antioxidant, anti-HIV, anti-diabetes, anti-cholinesterase activity in vitro and in silico. The C. uredinicola extract showed flavonoids, tannins, alkaloids, glycosides, phenols, terpenoids, and coumarins presence in qualitative method. From GC-MS analysis, identified seven different phytochemicals and out of seven, four (coumarin, coumarilic acid, hymecromone, alloisoimperatorin) are coumarins. The C. uredinicola extract have shown significant antioxidant activity in DPPH (73) and FRAP (1359) method. The HIV-1 RT (83.81+2.14), gp 120 (80.24+2.31), integrase (79.43+3.14) and protease (77.63+2.14), DPPIV, β-glucosidase and acetyl cholinesterase activity was significantly reduced by the extract. The 2-diphenylmethyleneamino methyl ester had shown significant interaction with oxidant and HIV-1 proteins whereas alloisoimperatorin have interacted with diabetes and cholinesterase proteins followed by hymecromone with high binding energy. These three phytochemicals are non-carcinogens, non-toxic, readily degradable and have drug likeliness properties. The C. uredinicola phytochemicals are responsible for management of diabetes, HIV-1 and Alzheimer. Further in vivo work is needed to justify our research.


Blood ◽  
1975 ◽  
Vol 46 (1) ◽  
pp. 51-64 ◽  
Author(s):  
AE Gassmann ◽  
R van Furth

Abstract The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24–48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.


2021 ◽  
Vol 118 (46) ◽  
pp. e2104721118
Author(s):  
Dominic Paquin-Proulx ◽  
Kerri G. Lal ◽  
Yuwadee Phuang-Ngern ◽  
Matthew Creegan ◽  
Andrey Tokarev ◽  
...  

Acute HIV-1 infection (AHI) results in the widespread depletion of CD4+ T cells in peripheral blood and gut mucosal tissue. However, the impact on the predominantly CD4+ immunoregulatory invariant natural killer T (iNKT) cells during AHI remains unknown. Here, iNKT cells from peripheral blood and colonic mucosa were investigated during treated and untreated AHI. iNKT cells in blood were activated and rapidly depleted in untreated AHI. At the time of peak HIV-1 viral load, these cells showed the elevated expression of cell death–associated transcripts compared to preinfection. Residual peripheral iNKT cells suffered a diminished responsiveness to in vitro stimulation early into chronic infection. Additionally, HIV-1 DNA, as well as spliced and unspliced viral RNA, were detected in iNKT cells isolated from blood, indicating the active infection of these cells in vivo. The loss of iNKT cells occurred from Fiebig stage III in the colonic mucosa, and these cells were not restored to normal levels after initiation of ART during AHI. CD4+ iNKT cells were depleted faster and more profoundly than conventional CD4+ T cells, and the preferential infection of CD4+ iNKT cells over conventional CD4+ T cells was confirmed by in vitro infection experiments. In vitro data also provided evidence of latent infection in iNKT cells. Strikingly, preinfection levels of peripheral blood CD4+ iNKT cells correlated directly with the peak HIV-1 load. These findings support a model in which iNKT cells are early targets for HIV-1 infection, driving their rapid loss from circulation and colonic mucosa.


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