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1.
PLoS Pathog ; 15(6): e1007840, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31173604

RESUMO

BLyS/BAFF is recognized for its role in B-cell ontogenesis, as well as cell fate decision towards the first-line/innate marginal zone (MZ) B-cell pool. Excess BLyS/BAFF is associated with hyperglobulinemia and increased frequencies of activated precursor-like MZ B-cells. Herein, we show that HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs) had lower soluble BLyS/BAFF levels and relative frequencies of BLyS/BAFF expressing cells in their genital mucosa when compared to those from HIV-infected CSWs and HIV-uninfected non-CSWs. Furthermore, we identified genital innate and/or marginal zone (MZ)-like CD1c+ B-cells that naturally bind to fully glycosylated gp120, which frequencies were lower in HESNs when compared to HIV-infected CSWs and HIV-uninfected non-CSWs. Although genital levels of total IgA were similar between groups, HESNs had lower levels of total IgG1 and IgG3. Interestingly, HIV-gp41 reactive IgG1 were found in some HESNs. Low genital levels of BLyS/BAFF observed in HESNs may allow for controlled first-line responses, contributing to natural immunity to HIV.


Assuntos
Antígenos CD1/imunologia , Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Genitália Feminina/imunologia , Glicoproteínas/imunologia , Soronegatividade para HIV/imunologia , HIV-1/imunologia , Imunidade Inata , Profissionais do Sexo , Adulto , Linfócitos B/patologia , Feminino , Anticorpos Anti-HIV/imunologia , Humanos , Imunoglobulina G/imunologia , Pessoa de Meia-Idade
2.
Anal Biochem ; 535: 43-46, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28778493

RESUMO

Copper is essential for numerous physiological functions, and copper compounds may display therapeutic as well as cytotoxic effects. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay is a standard test largely used in cytotoxicity studies. This report shows that low micromolar levels of copper compounds such as Cu(II)Urea2, Cu(II)Ser2 and CuCl2 can interfere with the MTT assay making improper the detection of formazan product of MTT reduction. Comparatively, the Neutral Red assay appears to be sensitive and showing no interference with these compounds. The lactate dehydrogenase alternative assay cannot be used because of inhibitory effect of these copper compounds on the enzyme activity.


Assuntos
Bioensaio , Cobre/farmacologia , Vermelho Neutro/química , Compostos Organometálicos/farmacologia , Sais de Tetrazólio/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cobre/química , Camundongos , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química , Ureia/farmacologia
3.
Int J Infect Dis ; 136: 136-145, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37717649

RESUMO

BACKGROUND: Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear. METHODS: In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. RESULTS: COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P <0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs post-vaccination: 1.89 ± 1.12; P <0.001), and increases in World Health Organization (WHO)-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs post-vaccination: 56.15 ± 22.83; P <0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1ß, and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity toward SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination. CONCLUSIONS: Our study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.


Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Prospectivos , SARS-CoV-2 , Vacinação , Citocinas , Inflamação , Imunidade , Quimiocinas
4.
Viruses ; 14(2)2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35215954

RESUMO

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting "tolerogenic" monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5-5 years CSWs herein termed "early HESNs"), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.


Assuntos
Soronegatividade para HIV/imunologia , HIV-1/imunologia , Monócitos/imunologia , Profissionais do Sexo/estatística & dados numéricos , Adulto , Fatores de Restrição Antivirais/genética , Fatores de Restrição Antivirais/metabolismo , Benin/epidemiologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Resistência à Doença/imunologia , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Infecções por HIV/imunologia , Humanos , Pessoa de Meia-Idade , Monócitos/metabolismo
5.
Viruses ; 10(4)2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29690575

RESUMO

Africa accounts for the majority of global human immunodeficiency virus (HIV) infections, most of which affect women through heterosexual intercourse. Currently, there is no cure for HIV and the development of vaccines and microbicides remains the best solution to eradicate the pandemic. We and others have identified HIV highly-exposed seronegative (HESN) individuals among African female commercial sex workers (CSWs). Analyses of genital samples from HESNs have demonstrated potent innate and anti-inflammatory conditions, HIV-specific CD4⁺ and CD8⁺ T-cells as well as immunoglobulins (Igs), and increased regulatory cell populations, all of which support a delicate balance between strength and control against HIV intrusion. Moreover, we have recently shown that frequencies of innate marginal zone (MZ) B-cells are decreased in the blood of HESNs when compared to HIV-uninfected non-CSW women, suggesting their recruitment to peripheral sites. This coincides with the fact that levels of B lymphocyte stimulator (BLyS/BAFF), known to shape the MZ pool and whose overexpression leads to MZ deregulation in HIV-infected progressors, are significantly lower in the blood of HESNs when compared to both HIV-infected CSWs and HIV-uninfected non-CSW women. Interestingly, MZ B-cells can bind HIV gp120 and produce specific IgG and IgA, and have a propensity for B regulatory potential, which could help both the fight against HIV and maintenance of low inflammatory conditions in HESNs. HESN individuals provide an exceptional opportunity to identify important clues for the development of protective devices, and efforts should aim at soliciting immune responses observed in the context of their natural immunity to HIV.


Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/isolamento & purificação , Genitália Feminina/imunologia , Infecções por HIV/imunologia , HIV/imunologia , Imunidade Inata , Profissionais do Sexo , África , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Anticorpos Anti-HIV/análise , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia
6.
Sci Rep ; 6: 32318, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27561453

RESUMO

We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of "precursor" innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection. Therefore, we assessed blood BLyS levels and B-cell status in HIV highly-exposed commercial sex workers (CSWs) from Benin. We found blood BLyS levels of HIV-uninfected CSWs were lower than those observed in both HIV-infected CSW and HIV-uninfected non-CSW groups. Furthermore, levels of BLyS expression on blood T-cells and monocytes were lower in HIV-uninfected CSWs when compared to HIV-infected CSWs, but higher than those observed for HIV-uninfected non-CSWs. Concomitantly, HIV-infected CSWs presented a dysregulated blood B-cell compartment, characterized by increased total IgG1, increased frequencies of populations presenting immature and/or innate profiles and a higher ratio of IgG(+)/IgA(+) plasmablasts. In contrast, relatively low levels of BLyS in the blood of HIV-uninfected CSWs coincided with a rather preserved B-cell compartment.


Assuntos
Fator Ativador de Células B/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Imunidade Inata/imunologia , Profissionais do Sexo , Adulto , Fator Ativador de Células B/sangue , Linfócitos B/imunologia , Linfócitos B/metabolismo , Benin , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Carga Viral/imunologia
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