Abstract
A modified vaccinia Ankara-based HIV-1 vaccine clade B (MVA-B) has been tested for safety and immunogenicity in low-risk human immunodeficiency virus (HIV)-uninfected individuals and as a therapeutic vaccine in HIV-1-infected individuals on combined antiretroviral therapy (cART). As a therapeutic vaccine, MVA-B was safe and broadly immunogenic; however, patients still showed a viral rebound upon treatment interruption. Monocytes are an important part of the viral reservoir and several studies suggest that they are partly responsible for the chronic inflammation observed in cART-treated HIV-infected people. The CD300 family of receptors has an important role in several diseases, including viral infections. Monocytes express CD300a, c, e, and f molecules and lipopolysaccharide (LPS) and other stimuli regulate their expression. However, the expression and function of CD300 receptors on monocytes in HIV infection is still unknown. In this work, we investigated for the first time the expression of CD300 molecules and the cytokine production in response to LPS on monocytes from HIV-1-infected patients before and after vaccination with MVA-B. Our results showed that CD300 receptors expression on monocytes from HIV-1-infected patients correlates with markers of HIV infection progression and immune inflammation. Specifically, we observed a positive correlation between the expression of CD300e and CD300f receptors on monocytes with the number of CD4+ T cells of HIV-1-infected patients before vaccination. We also saw a positive correlation between the expression of the inhibitory receptor CD300f and the expression of CD163 on monocytes from HIV-1-infected individuals before and after vaccination. In addition, monocytes exhibited a higher cytokine production in response to LPS after vaccination, almost at the same levels of monocytes from healthy donors. Furthermore, we also described a correlation in the expression of CD300e and CD300f receptors with TNF-α production in response to LPS, only in monocytes of HIV-1-infected patients before vaccination. Altogether, our results describe the impact of HIV-1 and of the MVA-B vaccine in cytokine production and monocytes phenotype.
Highlights
The development of combined antiretroviral therapy has significantly improved the clinical outcome in human immunodeficiency virus (HIV)-infected patients
We observed a tendency, not statistically significant, of CD300c expression to decrease on monocytes of HIV-1-infected subjects [healthy donors (HD) median fluorescence intensity (MFI) = 2,717 ± 630.4 vs HIV MFI = 1,596 ± 465.5] (Figure 1A), especially in non-classical monocytes
Our results revealed that the expression pattern of CD300 molecules in monocytes from HD and in monocytes from HIV-1-infected people were not significantly different
Summary
The development of combined antiretroviral therapy (cART) has significantly improved the clinical outcome in human immunodeficiency virus (HIV)-infected patients. It has been described that monocytes of chronically HIV-infected subjects differ from monocytes of healthy people in subsets distribution [12], expression of different markers (e.g., CD163) [13], and cytokine production (e.g., IL-6) [11] All these findings emphasize the importance of studying the mechanisms that regulate the activation of monocytes in HIV-infected patients. In HIV-infected patients, the expression of the CD300a inhibitory receptor is down-regulated on B lymphocytes, which may help to explain the hyperactivation and dysfunction of B cells observed in these individuals [18]. We investigated the effect of the vaccination with MVA-B in the cytokine production of monocytes stimulated with LPS in HIV-infected subjects and we studied the correlation with the CD300 family of molecules expression. VL, viral load; ART, antiretroviral therapy; HIV, human immunodeficiency virus
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