Implicações clínicas e imunológicas dos micronutrientes durante a infecção pelo HIV

During HIV infection there is an alteration in the functions of the immune system and chronic inflammation that cannot be resolved with antiretroviral treatment (ART). Moreover, a high prevalence of micronutrient deficiencies has been reported in the HIV+ population due to an increase in their demand and excretion.    Such chronic inflammation and micronutrient deficiency is associated with comorbidities not linked to the acquired immunodeficiency syndrome (AIDS) such as high blood pressure, cardiovascular disease, metabolic syndrome, cancer, and osteoporosis. The development of strategies aimed at regulating the inflammation and chronic activation present in HIV+ patients receiving ART to improve their quality of life and decrease the prevalence of comorbidities. A promising option is nutritional intervention through supplementaltion of micronutrients that have shown to have a regulatory effect on inflammation and immune response and which could represent a safe and cost-effective option.Durante la infección por VIH existe una alteración en las funciones del sistema inmunológico e inflamación crónica que no logra resolverse con el tratamiento antirretroviral (TAR). Aunado a lo anterior, se ha reportado una alta prevalencia de deficiencia de micronutrientes en la población VIH+ debido a un aumento en la demanda y en la excreción de los mismos.   Dicha inflamación crónica y deficiencia de micronutrientes está asociada a la aparición de comorbilidades no asociadas al síndrome de inmunodeficiencia adquirida (SIDA) como hipertensión arterial, enfermedades cardiovasculares, síndrome metabólico, cáncer y osteoporosis. Es necesario desarrollar estrategias dirigidas a regular la inflamación y activación crónica presente en los individuos VIH+ bajo TAR para mejorar su calidad de vida y disminuir la prevalencia de comorbilidades. Una opción prometedora es la intervención nutricional a través de la suplementación de micronutrientes que han demostrado tener un efecto regulador de la inflamación y de la respuesta inmunológica y que podrían representar una opción segura y costo eficiente.Durante a infeção pelo HIV, há uma alteração nas funções do sistema imunológico e uma inflamação crônica que não se podem resolver com o tratamento antirretroviral (TAR). Além disso, se tem registado uma alta prevalência de deficiência de micronutrientes na população HIV+ devido a um aumento no seu consumo e na sua excreção.   Essa inflamação crônica e deficiência de micronutrientes estão associadas ao aparecimento de comorbilidades não associadas à SIDA, como hipertensão arterial, doenças cardiovasculares, síndrome metabólico, câncer e osteoporose. É necessário desenvolver estratégias destinadas a regular a inflamação e a ativação crônica presentes em indivíduos HIV+ sob TAR para melhorar sua qualidade de vida e diminuir a prevalência de comorbilidades. Uma opção promissora é a intervenção nutricional através da suplementação de micronutrientes que demonstraram ter um efeito regulador na inflamação e na resposta imunológica e que poderiam representar uma opção segura e de baixo custo

Reduced naïve CD8+T-cell priming efficacy in elderly adults

International audienceAging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8 + T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling na€ ıve CD8 + T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8 + T-cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8 + T-cell responses specific for a model antigen. Reduced CD8 + T-cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the na€ ıve CD8 + T-cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging

ART-naive and short-term ART experienced individuals have decreased frequency of CD161-expressing gut homing CD8+ T-cells.

<p>Frequencies (expressed as percentages) of peripheral blood (PB) memory gut homing (CD45RO+ CCR9+ B7+) CD4+ (A) and CD8+ (C) T-cells expressing CD161 were determined by flow cytometry on PBMCs of HIV-infected individuals (HIV+), antiretroviral (ART) naïve (n = 18), ART experienced individuals on short-term (n = 15) and long-term treatment (n = 32), HIV controllers (n = 6) and HIV seronegative individuals (SN, n = 5). Scatter plots were used to represent the data. Horizontal lines indicate median values. Each symbol represents one individual. The red symbols represent the females in each group. Groups were compared using Kruskal-Wallis test correcting for multiple comparisons using the Dunnett´s post-test. Only significant corrected p values are shown ***p<0.0005, **p<0.005, *p<0.05. Spearman's rank correlation between PB gut homing CD4+ CD161+ T-cells and plasma viral load (pVL) in the ART naive group (B). Gender was color-coded as follows: red dots, women and black dots, men.</p

The frequency of PB gut homing CD4+ and CD8+ T-cells is altered in HIV infection.

<p>Frequencies (expressed as percentages) of peripheral blood (PB) memory gut homing (CD45RO+ CCR9+ β7+) CD4+ (A) and CD8+ (B) T-cells was determined by flow cytometry on PBMCs of HIV-infected individuals (HIV+), antiretroviral (ART) naïve (n = 18), ART experienced individuals on short-term (n = 15) and long-term treatment (n = 32), HIV controllers (n = 6) and HIV seronegative individuals (SN, n = 5). Scatter plots were used to represent the data. Horizontal lines indicate median values. Each symbol represents one individual. The red symbols represent the females in each group. Groups were compared using Kruskal-Wallis test correcting for multiple comparisons using the Dunnett´s post-test. Only significant corrected p values are shown ***p<0.0005, **p<0.005, *p<0.05. Gender was color-coded as follows: red dots, women and black dots, men.</p

The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection

Abstract Background Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. Results We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. Conclusion We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status

Gating strategy.

<p>The gating strategy used for all the samples was to first define singlet and morphology by using forward versus side scatter, followed by the exclusion of dead cells (aqua dye negative events) and the exclusion of CD14, CD19, CD56, CD11c and CD123 positive cells (dump gate). Live cells were gated on CD3+ and CD45RO+ cells. Next, CCR9+ and/or β7+ cells were gated and defined as gut homing T-cells. Then CD4+ and CD8+ T cells were gated and finally the expression of CD161 on the gut homing CD4+ (top) and CD8+ (bottom) T-cells was gated. T cell activation was determined by the simultaneous expression of CD38 and HLADR on gut homing CD4+ and CD8+ T cells.</p

Immunodominance of HLA-B27-restricted HIV KK10-specific CD8(+) T-cells is not related to naïve precursor frequency

International audienceThe factors that determine the immunodominance, efficacy and almost ubiquitous presence of CD8(+) T-cell responses to the HLA-B27-restricted HIV-1 p24 Gag-derived KK10 epitope remain to be fully elucidated. Here, we show that neither the precursor frequency nor the priming capacity of KK10-reactive CD8(+) T-cells within the naïve pool differ substantially in comparison to other specificities. These data implicate alternative mechanisms in the relative protection conferred by CD8(+) T-cell responses to this epitope

Serum Levels of IFABP2 and Differences in Lactobacillus and Porphyromonas gingivalis Abundance on Gut Microbiota Are Associated with Poor Therapeutic Response in Rheumatoid Arthritis: A Pilot Study

Intestinal dysbiosis is related to the physiopathology and clinical manifestation of rheumatoid arthritis (RA) and the response to pharmacologic treatment. The objectives of this study were (1) to analyze the effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the abundance of gut microbiota&rsquo;s bacteria; (2) to evaluate the relationship between the differences in microbial abundance with the serum levels of intestinal fatty-acid binding protein 2 (IFABP2), cytokines, and the response phenotype to csDMARDs therapy in RA. A cross-sectional study was conducted on 23 women diagnosed with RA. The abundance of bacteria in gut microbiota was determined with qPCR. The ELISA technique determined serum levels of IFABP2, TNF-&alpha;, IL-10, and IL-17A. We found that the accumulated dose of methotrexate or prednisone is negatively associated with the abundance of Lactobacillus but positively associated with the abundance of Bacteroides fragilis. The Lactobacillus/Porphyromonas gingivalis ratio was associated with the Disease Activity Score-28 for RA with Erythrocyte Sedimentation Rate (DAS28-ESR) (r = 0.778, p = 0.030) and with the levels of IL-17A (r = 0.785, p = 0.027) in the group treated with csDMARD. Moreover, a relation between the serum levels of IFABP2 and TNF-&alpha; (r = 0.593, p = 0.035) was observed in the group treated with csDMARD. The serum levels of IFABP2 were higher in patients with secondary non-response to csDMARDs therapy. In conclusion, our results suggest that the ratios of gut microbiota&rsquo;s bacteria and intestinal permeability seems to establish the preamble for therapeutic secondary non-response in RA

Serum Levels of IFABP2 and Differences in <i>Lactobacillus</i> and <i>Porphyromonas gingivalis</i> Abundance on Gut Microbiota Are Associated with Poor Therapeutic Response in Rheumatoid Arthritis: A Pilot Study

Intestinal dysbiosis is related to the physiopathology and clinical manifestation of rheumatoid arthritis (RA) and the response to pharmacologic treatment. The objectives of this study were (1) to analyze the effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the abundance of gut microbiota’s bacteria; (2) to evaluate the relationship between the differences in microbial abundance with the serum levels of intestinal fatty-acid binding protein 2 (IFABP2), cytokines, and the response phenotype to csDMARDs therapy in RA. A cross-sectional study was conducted on 23 women diagnosed with RA. The abundance of bacteria in gut microbiota was determined with qPCR. The ELISA technique determined serum levels of IFABP2, TNF-α, IL-10, and IL-17A. We found that the accumulated dose of methotrexate or prednisone is negatively associated with the abundance of Lactobacillus but positively associated with the abundance of Bacteroides fragilis. The Lactobacillus/Porphyromonas gingivalis ratio was associated with the Disease Activity Score-28 for RA with Erythrocyte Sedimentation Rate (DAS28-ESR) (r = 0.778, p = 0.030) and with the levels of IL-17A (r = 0.785, p = 0.027) in the group treated with csDMARD. Moreover, a relation between the serum levels of IFABP2 and TNF-α (r = 0.593, p = 0.035) was observed in the group treated with csDMARD. The serum levels of IFABP2 were higher in patients with secondary non-response to csDMARDs therapy. In conclusion, our results suggest that the ratios of gut microbiota’s bacteria and intestinal permeability seems to establish the preamble for therapeutic secondary non-response in RA