HIV Nef promotes expression of B-lymphocyte stimulator by blood dendritic cells during HIV infection in humans.

Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS; also known as "B-cell factor belonging to the tumor necrosis factor family" [BAFF]). We have recently shown that, in human immunodeficiency virus (HIV)-infected individuals with rapid and those with classic disease progression, B-cell dysregulations were associated with increased BLyS expression in plasma and by blood myeloid DCs (mDCs), in contrast to aviremic HIV-infected individuals with slow disease progression (also known as "elite controllers"). In previous work with transgenic mice expressing HIV genes, B-cell dysregulations were concomitant with altered mDCs and dependent on HIV negative factor (Nef). We now report that HIV Nef is detected early after infection and despite successful therapy in plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and classic progressors, whereas it is low to undetectable in aviremic slow progressors. In vitro, HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a process involving STAT1. Importantly, this is counteracted in the presence of all-trans retinoic acid. Nef thus contributes to high BLyS proinflammatory profiles in HIV-infected individuals.

Weight changes in overweight children enrolled in a therapeutic education program.

BACKGROUND: Between 2016 and 2018, overweight children in the Midi-Pyrénées region of France were invited to participate in the Tout sur l'EQuilibre Alimentaire et l'Activité Physique (TEQAAP; All About Balanced Eating and Physical Activity) education program offered by the Structure d'Expertise Régionale Obésité Occitanie (SEROO; Regional Expert Center for Obesity in Occitanie). OBJECTIVES: To describe the patient population and evaluate the program efficacy. The primary criterion was the body mass index (BMI) Z-score of the patients at the end of the program compared to the beginning. METHODS: This retrospective, descriptive, and analytical study included 262 children (mean age: 10 years+10 months; 64% female) between 1 January 2016 and 31 December 2018. Data from 138 patients (52.7%) were accessible and analyzed. The mean study duration was 9 months. RESULTS: The mean BMI at inclusion was 23.3 kg/m² with a mean Z-score of 2.8 ± 0.6; 82% were overweight, 11.1% were obese, and 6.1% were normal weight. Socioeconomic categories were well-balanced (35% high, 28% intermediate, 37% low). At the end of the study, 87% of the children had improved or stabilized their BMI, and Z-scores were lower by 9%±2 (p<0.001). CONCLUSION: The TEQAAP program led to an improvement in the BMI of overweight children.

Fluctuations in Blood Marginal Zone B-Cell Frequencies May Reflect Migratory Patterns Associated with HIV-1 Disease Progression Status.

We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate "precursor" marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis. We have therefore longitudinally measured plasma levels of B-tropic chemokines by ELISA-based technology as well as their ligands by flow-cytometry on blood B-cell populations of HIV-1-infected individuals with different rates of disease progression and uninfected controls. Migration potential of B-cell populations from these individuals were determined by chemotaxis assays. We found important modulations of CXCL13-CXCR5, CXCL12-CXCR4/CXCR7, CCL20-CCR6 and CCL25-CCR9 chemokine-axes and increased cell migration patterns in HIV progressors. Interestingly, frequencies of CCR6 expressing cells were significantly elevated within the precursor MZ-like population, consistent with increased migration in response to CCL20. Although we found little modulation of chemokine-axes in EC, cell migration was greater than that observed for uninfected controls, especially for MZ-like B-cells. Overall the immune response against HIV-1 may involve recruitment of MZ-like B-cells to peripheral sites. Moreover, our findings suggest that "regulated" attraction of these cells in a preserved BLyS/BAFF non-inflammatory environment, such as encountered in EC could be beneficial to the battle and even control of HIV.