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1.
Int Immunopharmacol ; 140: 112765, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39083931

ABSTRACT

BACKGROUND: Previous studies have shown that failure to control inflammatory processes mediated by regulatory T (Treg) cells contributes to chronic obstructive pulmonary disease (COPD) development and progression. The activity of Treg cells depends on their phenotypic characteristics: resting Treg (rTreg, CD3+CD4+CD25+FOXP3+CD25++CD45RA+) and activated Treg (aTreg, CD3+CD4+CD25+FOXP3+CD25+++CD45RA-) cells exhibit immunosuppressive activity, while cytokine-secreting T cells (FrIII, CD3+CD4+CD25+FOXP3+CD25++CD45RA-) exhibit proinflammatory activity. Previous findings have shown an increased density of cytokine-secreting T cells in COPD patients experiencing exacerbation. However, the methods for evaluating COPD under stable conditions are lacking. AIM: To evaluate Treg cell phenotypes in patients with different stages of COPD under stable conditions. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from non-obstructed smokers and ex-smokers (NOS group, n = 19) and COPD patients at different stages (COPD I-II group, n = 25; COPD III-IV group, n = 25). The phenotypic characteristics of Treg cells and Th17 cells and their respective intracellular cytokines were analyzed by flow cytometry. RESULTS: Both obstructed groups showed an increase in the proportion of rTregs, while the COPD III-IV group showed additional increases in total Treg and Th17 cells and in IL-10+ cells. There was an increase in proinflammatory mediators (CD3+CD4+IL-17+ cells; CD3+CD4+RORγt+ cells) in the COPD I-II group. In contrast, the NOS group demonstrated high proportions of proinflammatory Treg cells and proinflammatory CD8+ T cells (CD3+CD8+IL-17+). CONCLUSION: Despite the increase in both total Treg cells and the rTreg phenotype from the early stages of COPD, there was a decrease in cells expressing IL-10, suggesting a failure in controlling the inflammatory process. These events precede the progression of the inflammatory process mediated by Th17 cells.


Subject(s)
Pulmonary Disease, Chronic Obstructive , T-Lymphocytes, Regulatory , Humans , Pulmonary Disease, Chronic Obstructive/immunology , T-Lymphocytes, Regulatory/immunology , Male , Aged , Middle Aged , Female , Phenotype , Th17 Cells/immunology , Cytokines/metabolism , Smoking/immunology
2.
Scand J Immunol ; 97(3): e13247, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36541819

ABSTRACT

SARS-CoV-2 triggers inflammasome-dependent release of pro-inflammatory cytokine IL-1ß and pyroptosis, therefore, contributes to the huge inflammatory response observed in severe COVID-19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID-19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID-19 patients and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID-19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID-19 pathogenesis.


Subject(s)
COVID-19 , Inflammasomes , Humans , NLR Family, Pyrin Domain-Containing 3 Protein , Neutrophils , SARS-CoV-2 , Interleukin-1beta
3.
Inflamm Res ; 72(10-11): 1933-1940, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36416944

ABSTRACT

OBJECTIVE AND DESIGN: The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease. METHODS: To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B, and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients. RESULTS: The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases. CONCLUSION: Inflammasome genetic background contributes to individual response to SARS-CoV-2.


Subject(s)
COVID-19 , Inflammasomes , Humans , Inflammasomes/genetics , Inflammasomes/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , COVID-19/genetics , NLR Proteins/genetics , SARS-CoV-2/metabolism , Neoplasm Proteins/genetics , CARD Signaling Adaptor Proteins/genetics
4.
Antioxidants (Basel) ; 11(9)2022 Aug 29.
Article in English | MEDLINE | ID: mdl-36139764

ABSTRACT

The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.

5.
J Infect Dis ; 225(3): 510-519, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34355765

ABSTRACT

Vertical transmission is the main mechanism of human immunodeficiency virus type 1 (HIV-1) infection in infants, who may develop high viremia and rapidly progress to AIDS. Innate immunity agonists can control HIV-1 replication in vitro, but the protective effect in the neonatal period remains unknown. Herein, we evaluated the immunomodulatory and antiviral effects of type I interferon (IFN-I) adjuvants on cord blood monocyte-derived macrophages upon HIV-1 infection. Despite the phenotypic and transcriptional similarities between cord blood and adult macrophages, cord blood cells were prone to viral replication when infected with HIV-1. However, treatment with CL097 efficiently promoted the antiviral and inflammatory responses and inhibited HIV-1 replication in cord blood cells in an NF-κB and autophagy activation-independent manner. Our data suggest that cord blood macrophages are able to establish antiviral responses induced by IFN-I adjuvants similar to those of their adult counterparts, revealing a potential adjuvant candidate to enhance the neonatal immune response.


Subject(s)
HIV Infections , HIV-1 , Adjuvants, Immunologic , Adult , Antiviral Agents , Fetal Blood , Humans , Infant, Newborn , Macrophages , Toll-Like Receptor 7 , Toll-Like Receptor 8
6.
Exp Dermatol ; 31(2): 191-201, 2022 02.
Article in English | MEDLINE | ID: mdl-34358352

ABSTRACT

BACKGROUND: Methylisothiazolinone (MI) and Methylchloroisothiazolinone (MCI) are among the most common skin sensitizers, yet the immunological events that occur during MCI/MI allergic contact dermatitis (ACD) are still poorly understood. OBJECTIVES: To analyse dendrocytes, macrophage subtypes and T cells in skin during the elicitation phase of MCI/MI ACD. METHODS: Thirteen patients with positive patch test reactions to MCI/MI (ACD group) and 11 individuals with negative patch test results were selected. Skin biopsies were only performed at 48 hours of patch testing. Immunohistochemistry was conducted to assess T cells, dendrocytes (Factor XIIIa), M1 (p-Stat1, CD68) and M2 (c-Maf, CD163) macrophages. Transcriptional analyses were performed for cytokines and related factors, and further compared to atopic dermatitis samples (n=4). Immunofluorescence assays addressed T cells location, along with IL-4 or IL-13, within the skin. RESULTS: MCI/MI elicited dermal dendrocytes and macrophages, pronouncedly the M2 subtype. T cells, majorly CD4+ T cells, accumulated in the perivascular areas. Similarly, abundant IL-4 protein was detected in these areas. There was an upregulation of IL-4 and IL-13 mRNA expression, a mild increase in IFNG mRNA levels and a down-regulation of RORC in the ACD group. Immunofluorescence revealed dermal clusters of T cells co-localized with IL-4. CONCLUSIONS: M2 macrophages and Th2 cells participate in the immunopathogenesis of MCI/MI ACD. Dermal dendrocytes and M2 macrophages may assist the formation of CD4+ T cells perivascular clusters. These findings render a mechanistic insight into the MCI/MI reaction. Further analysis at different timepoints of patch testing is required to fully comprehend this ACD kinetics.


Subject(s)
Dermatitis, Allergic Contact , Interleukin-4 , Humans , Interleukin-13 , Macrophages , Patch Tests/adverse effects , Patch Tests/methods , RNA, Messenger , Th2 Cells , Thiazoles
7.
J Neuroimmunol ; 360: 577697, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34461359

ABSTRACT

Zika virus (ZIKV) infection has been associated with the development of Neuromyelitis Optica Spectrum Disorder (NMOSD). ZIKV-induced antibodies that putatively cross-react to aquaporin-4 (AQP4) protein are suggested to cause inflammation of the optic nerve. A region of similarity between AQP4 and the ZIKV NS2B protein was identified. Our data showed that ZIKV-associated NMOSD patients develop anti-AQP4 antibodies, but not anti-ZIKV NS2B antibodies, revealing that cross-reacting antibodies are not the underlying cause of this phenotype. ZIKV infection in mice showed persistent viral replication in the eye tissue, suggesting that NMOSD symptoms are consequence of viral infection of the optic nerve cells.


Subject(s)
Antibodies, Viral/immunology , Aquaporin 4/immunology , Autoantibodies/immunology , Neuromyelitis Optica/immunology , Zika Virus/immunology , Animals , Antibodies, Viral/blood , Autoantibodies/blood , Cross Reactions , Epitopes/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Mice , Mice, Inbred C57BL , Molecular Mimicry , Neuromyelitis Optica/etiology , Optic Nerve/virology , Viral Nonstructural Proteins/immunology , Virus Replication , Zika Virus/physiology , Zika Virus Infection/complications , Zika Virus Infection/immunology , Zika Virus Infection/virology
9.
Oncotarget ; 9(3): 3497-3506, 2018 Jan 09.
Article in English | MEDLINE | ID: mdl-29423061

ABSTRACT

Sézary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sézary cells have been studied extensively, studies on adaptive immunity regarding CD8+T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Rα axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum. Although the SS patients of our cohort had reduced numbers of CD8+ T cells, they exhibited higher percentages of CD8+CD38+ T cells, mainly effector/memory CD8+ T cells, than the control group. In contrast, down-regulated expression of the activation markers CD127/IL-7R and CD26 was found in the CD8+ T cells of SS patients. High serum levels of sCD38 and sCD127 and scarce serum levels of IL-7 were detected, emphasizing the immune activation status of SS patients. Moreover, CD8+ T cells from SS patients exhibited IL-7 unresponsiveness to STAT5 phosphorylation and Bcl-2 expression, and IL-7 priming partially restored IFNγ production. Our findings showed a chronic activation profile of CD8+ T cells, as an attenuated cytotoxic profile and impaired IL-7 responsiveness was observed, suggesting chronic activation status of CD8+ T cells in SS patients.

10.
Int J Dermatol ; 57(4): 434-440, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29355930

ABSTRACT

INTRODUCTION: Our group recently demonstrated that IgG modulates αßT cell cytokine production during the maturation process in the human thymus. The effects of this modulation are IgG repertoire dependent and can exert a systemic and long-term impact. OBJECTIVE: To investigate whether IgG from atopic dermatitis (AD) patients can modulate cytokine production of infant intrathymic TCD4 and TCD8 cells in vitro. METHODS: Thymic tissues were obtained from newborn children from nonatopic mothers, and thymocytes were cultured for 6 days with purified IgG from AD patients or with intravenous immunoglobulin (IVIG) or mock conditions as controls. Cells were gated as double positive T cells (TDP- CD4+ CD8+ ), TCD4 cells (CD4+ CD8- ), or TCD8 cells (CD4- CD8+ ), and intracellular levels of IL-17A, IFN-γ, TNF-α, IL-4, IL-10, and TGF-ß were evaluated by flow cytometry. RESULTS: Compared to mock and IVIG culture conditions, IgG of AD individuals induced in vitro intracellular production of IL-17 and IL-10 by intrathymic TDP, TCD4, and TCD8 cells of infants. TGF-ß was also detected at a higher frequency in response to AD IgG in TDP and TCD8 cells compared to mock and IVIG cultured conditions. An opposite effect was detected upon IFN-γ production in TCD4 cells, such that AD IgG reduced IFN-γ production compared to production under mock conditions but not under IVIG conditions. CONCLUSION: IgG of AD patients can stimulate cytokine production in infant thymocytes and thus resembles the peripheral profile observed in adults. These findings suggest a novel mechanism that can contribute to AD pathogenesis.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cytokines/biosynthesis , Immunoglobulin G/pharmacology , Protein Biosynthesis/drug effects , Adult , Cells, Cultured , Dermatitis, Atopic/blood , Humans , Immunoglobulin G/blood , Immunoglobulins, Intravenous/pharmacology , Infant, Newborn , Interferon-gamma/biosynthesis , Interleukin-10/biosynthesis , Interleukin-17/biosynthesis , Interleukin-4/biosynthesis , Thymocytes , Thymus Gland/cytology , Transforming Growth Factor beta/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis
11.
Oncotarget ; 8(54): 92183-92194, 2017 Nov 03.
Article in English | MEDLINE | ID: mdl-29190907

ABSTRACT

Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation. We observed preserved CD56bright NK cells and a low percentage of CD56dim NK cells in the peripheral blood of SS patients compared to those in the healthy control group. Both NK cell populations showed down-modulation of NKG2C and NKG2D expression, which was associated with high serum levels of the soluble form of NKG2D ligands. In contrast, an expansion of "memory" CD57+ NKG2C+ NK cells and high cytomegalovirus antibody titers were detected in SS patients. Profiling of the TLR signaling genes in NK cells from SS patients showed an abundance of differentially expressed genes (DEGs) in NK cells in the unstimulated condition, with mostly up-regulation of NFκB/JNK p38 pathway genes, but there was down-regulation of type I (IFN-α/ß) and II (IFN-γ) interferon and IL-12A. After activation of NK cells with TLR7/8 agonist, the down-regulated genes correlated with the IFN response, and IL-12 became up-regulated, together with other antitumor factors. NK cell activation with a dual agonist for TLR7 and TLR8 is able to induce the expression of IFN-γ and type I IFN, which can improve immunity in SS patients.

12.
Sci Rep ; 7(1): 524, 2017 04 03.
Article in English | MEDLINE | ID: mdl-28373665

ABSTRACT

Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56bright and CD56dim cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners. TLR3-induced expression of IFN-γ, TNF and CD107a by polyfunctional CD56bright NK cells was more pronounced in ESN individuals than that in healthy controls. Activated NK cells, as determined by CD38 expression, were increased only in the HIV-1-infected partners, with reduced IFN-γ and CD107a expression. Moreover, CD38+ NK cells of the HIV-1-infected partners were associated with increased expression of inhibitory molecules, such as NKG2A, PD-1 and Tim-3, while NK cells from ESN subjects showed decreased NKG2A expression. Altogether, these findings indicate that NK cells of ESN individuals were highly responsive to TLR3 activation and had a polyfunctional NK cell phenotype, while the impaired TLR3 response in HIV-1-infected partners was associated with an inhibitory/exhaustion NK cell phenotype.


Subject(s)
HIV Infections/immunology , HIV Infections/metabolism , HIV Seronegativity/immunology , HIV-1/immunology , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Lymphocyte Activation/immunology , Toll-Like Receptor 3/agonists , Biomarkers , CD56 Antigen/metabolism , Cytokines/metabolism , HIV Infections/virology , Humans , Immunophenotyping , L-Selectin/metabolism , Lymphocyte Count , Phenotype
13.
Int J Dermatol ; 56(6): 630-635, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28083892

ABSTRACT

BACKGROUD: Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and xerosis. Dendritic cells (DC) play an essential role in tissue inflammation in atopic dermatitis (AD) skin, especially the inflammatory epidermal dendritic cells (IDEC), a particular subset of myeloid dendritic cells (mDC). The aim of the present study was to assess the phenotype and function of mDC and circulating IDEC-like in peripheral blood mononuclear cells (PBMC) of adults with AD. METHODS: We selected 21 AD patients and 21 non-AD controls, age and gender matched. Expressions of FcεRI, CD36, TNF, IFN- γ, and IL-10 in mDC were analyzed by flow cytometry under various stimuli, such as staphylococcal enterotoxin B (SEB), TLR2 (Pam3CSK4), TLR4 (LPS), and TLR7/8 (CL097) agonists. RESULTS: The most prominent findings in AD patients were: (i) enhanced frequency of IL-10 under TLR4 (LPS), and decreased frequency of IFN-γ and TNF under TLR2 (Pam3CSK4) and 7/8 (CL097) stimulation in classic mDC; (ii) elevation of circulating IDEC-like frequency with TLR2 (Pam3CSK4) stimuli, augmented frequency of IFN-γ in nonstimulated condition, and of IL-10 under TLR7/8 (CL097) stimuli in IDEC-like population. CONCLUSIONS: In AD individuals, classic mDC showed an immunomodulatory profile, favoring tolerance in a combined action with IDEC-like, and inducing Th1 polarization. Our findings indicate a potential role of IDEC-like in the maintenance of inflammation in atopic dermatitis patients; moreover, IDEC-like may exert a regulatory impact on T cells of AD individuals through IL-10, often induced by agonist mimicking single stranded RNA virus.


Subject(s)
Dendritic Cells/immunology , Dendritic Cells/metabolism , Dermatitis, Atopic/immunology , Adolescent , Adult , CD36 Antigens/metabolism , Case-Control Studies , Cells, Cultured , Female , Humans , Imidazoles/pharmacology , Interferon-gamma/metabolism , Interleukin-10/metabolism , Leukocytes, Mononuclear , Lipopeptides/pharmacology , Lipopolysaccharides/pharmacology , Male , Middle Aged , Phenotype , Quinolines/pharmacology , Receptors, IgE/metabolism , Toll-Like Receptor 2/agonists , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 7/agonists , Toll-Like Receptor 8/agonists , Tumor Necrosis Factor-alpha/metabolism , Young Adult
14.
Oncotarget ; 7(46): 74592-74601, 2016 11 15.
Article in English | MEDLINE | ID: mdl-27780938

ABSTRACT

Sézary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists. IFN-γ was scarcely produced upon TLR activation in SS cells, albeit TLR 7/8 (CL097) enhanced their secretion at lower levels than the control group. TLR9 agonist efficiently induced IFN-I in SS patients, although this positive regulation was not observed for other cytokines, in direct contrast to the broad activity of CL097. Among the TLR agonists, TLR4 was able to induce pro-inflammatory, IL-10 and Th2 secretion, while TLR7-8 agonist induced the inflammatory cytokines, IFN-I and IFN-γ. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists.


Subject(s)
Cytokines/metabolism , Inflammation Mediators/metabolism , Interferon Type I/metabolism , Sezary Syndrome/metabolism , Toll-Like Receptors/agonists , Aged , Cytokines/blood , Female , Humans , Immunity, Innate , Inflammation Mediators/blood , Interferon Type I/blood , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Sezary Syndrome/blood , Sezary Syndrome/immunology
15.
Sci Rep ; 6: 25875, 2016 05 11.
Article in English | MEDLINE | ID: mdl-27168019

ABSTRACT

Individuals who remain HIV-seronegative despite repeated unprotected exposure to the virus are defined as exposed seronegative (ESN) individuals. Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility. The majority of HIV-1-infected individuals undergo antiretroviral therapy, which can decrease the level of HIV-1 exposure in ESNs. We analyzed type I interferon (IFN)-related antiviral and regulatory factors in peripheral blood mononuclear cells (PBMCs) and oral epithelial cells from serodiscordant couples. Our findings revealed that ESNs did not induce the expression of antiviral factors (APOBEC-3G, TRIM5-α, SAMDH1, STING, TBk1) or regulatory factors (Trex, Foxo3, Socs3, IL-10) in PBMCs, unlike their HIV-1-infected partners. In contrast, ESNs upregulated APOBEC-3G and type I/III IFNs (IFNs-α,-ß/-λ) in oral mucosal epithelial cells similar to their HIV-infected partners. The serodiscordant groups exhibited an increased expression of type I IFN-induced regulators, such as Trex and Foxo3, in oral epithelial cells. TLR7, TLR8 and TLR9 were expressed in oral epithelial cells of both ESNs and HIV-1-infected subjects. These findings revealed evidence of antiviral factors, type I/III interferon and regulatory factor expression only in the oral mucosal compartment of ESNs, while HIV-1-infected partners systemically and oral mucosal expressed the antiviral profile.


Subject(s)
Antiviral Agents/metabolism , HIV Infections/drug therapy , Interferon-alpha/metabolism , Interferon-beta/metabolism , Interferon-gamma/metabolism , Mouth/immunology , Adaptive Immunity , Adult , Epithelial Cells/cytology , Epithelial Cells/immunology , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , HIV Infections/immunology , HIV Infections/metabolism , HIV Seronegativity , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/virology , Male , Middle Aged , Mouth/cytology , Mouth/metabolism , Mouth/virology , Sexual Partners
16.
Sci Rep ; 5: 13883, 2015 Sep 08.
Article in English | MEDLINE | ID: mdl-26347358

ABSTRACT

Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38- T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.


Subject(s)
HIV-1/immunology , Lymphocyte Count , T-Lymphocyte Subsets/immunology , ADP-ribosyl Cyclase 1/metabolism , Adult , CD4 Lymphocyte Count , Cytokines/biosynthesis , Female , HIV Infections/blood , HIV Infections/immunology , Humans , Male , Middle Aged , Phenotype , T-Lymphocyte Subsets/metabolism , gag Gene Products, Human Immunodeficiency Virus/immunology
17.
Sci. rep ; 5: [13883], Sept. 2015. ilus
Article in English | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1016241

ABSTRACT

Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38- T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38- T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1


Subject(s)
Humans , T-Lymphocytes , HIV
18.
Int J Dermatol ; 54(8): 898-904, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25312705

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a chronic recurrent inflammatory disease, with prevalence of about 10-20% in children and 1-3% in adults. Staphylococcus aureus is present in 80-100% of skin from atopic patients and is related to worsening of the disease by the action of enterotoxins. The aim of this study was to evaluate the profile of anti-Staphylococcus aureus enterotoxin B (SEB) antibody isotypes and IgG subclass levels in adult AD. METHODS: We selected 38 patients with AD, diagnosed by Hanifin and Rajka's criteria, aged between 18 and 65, and 26 healthy controls (HC). The severity of the disease was established according to the Eczema Area and Severity Index and patients graded as mild (28%), moderate (58%), and severe (14%). Sera were assessed for IgG subclasses, IgA, IgM, and IgE against SEB by ELISA. RESULTS: Elevated circulating IgE and IgG4 anti-SEB antibody levels associated with decreased IgA and IgM levels were detected in patients with AD, when compared to HC individuals. The severity of AD was related to low IgG1 and IgG3 levels and a high IgE antibody response to SEB. Interestingly, absence of IgG4 response to SEB was lower in patients with AD (2.63%), when compared to controls (34.6%), while a similar absence was detected for IgG1 and IgE antibodies (AD, 23.3 and 18.4% vs. HC, 38.5 and 19.2%). CONCLUSION: Our findings evidenced a contributing role for IgG4 and IgE antibodies in AD pathogenesis, which are triggered by staphylococcal superantigens.


Subject(s)
Dermatitis, Atopic/immunology , Enterotoxins/immunology , Immunoglobulin E/blood , Immunoglobulin G/blood , Adolescent , Adult , Aged , Case-Control Studies , Female , Humans , Immunoglobulin A/blood , Immunoglobulin M/blood , Male , Middle Aged , Severity of Illness Index , Staphylococcus aureus , Young Adult
19.
J Acquir Immune Defic Syndr ; 67(5): 463-71, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25230289

ABSTRACT

BACKGROUND: Innate immunity, including natural killer (NK) cells, may play a significant role in maintaining natural resistance to infection in highly HIV-exposed seronegative (HESN) subjects. The differences between NK-cell subsets, regarding their activating/maturing marker expression and their memory markers, in HESN subjects are not fully defined. METHODS: We have conducted an analysis of the activating/memory markers and intracellular CD107a and interferon γ (IFN-γ) expression in NK-cell subsets from HESN and HIV-infected and healthy subjects. RESULTS: HESN individuals showed an increased expression of activating markers, such as NKG2D in CD56(bright) and CD56(dim) NK cells, and an increased frequency of CD56(bright)CD127⁺ and fully mature CD56(dim)CD57⁺ NK cells compared with HIV-infected patients and healthy control subjects. Of note, HESN individuals showed an increased frequency of memory CD56(dim)CD57⁺ NK cells, and this is known to be expanded on cytomegalovirus infection, as evidenced by their high rate of cytomegalovirus seropositivity. Simultaneous expression of the CD94, NKG2A, NKG2C, and NKG2D receptors on CD56(bright) NK cells was detected in HESN subjects, whereas in the HIV-1 group, the expression of these 4 receptors was enhanced in CD56(dim) NK cells. It was also found that CD56(bright) and CD56(dim) NK cells in HESN subjects showed increased CD107a and/or IFN-γ expression. CONCLUSIONS: The NK cells from HESN individuals presented a unique activation profile, with increased expression of NKG2D, CD107a, and IFN-γ and "memory" CD57⁺CD56(dim) NK cells. The complex network of functional NK-cell activities in HESN individuals may be exploited for long-term protection through vaccination.


Subject(s)
CD56 Antigen/analysis , HIV-1/immunology , Killer Cells, Natural/chemistry , Killer Cells, Natural/immunology , Lymphocyte Subsets/chemistry , Lymphocyte Subsets/immunology , NK Cell Lectin-Like Receptor Subfamily C/analysis , Adult , Aged , Female , Humans , Immunologic Memory , Interferon-gamma/analysis , Lysosomal-Associated Membrane Protein 1/analysis , Male , Middle Aged , Young Adult
20.
Lasers Med Sci ; 28(2): 451-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22415574

ABSTRACT

The effect of the low-level laser therapy (LLLT) in the modulation of cells related to inflammatory processes has been widely studied, with different parameters. The objective was to investigate the immediate and cumulative effect of infrared LLLT on chemokine monocyte chemotactic protein-1 (MCP-1) modulation in mice. Fifty-two isogenic mice were distributed in seven groups: control (n = 10, no surgical procedure), laser I (n = 7, surgical procedure and a single LLLT exposure 12 h after the surgery), laser II (n = 7, surgery followed by two LLLT exposures, 12 and 36 h after surgery), and laser III (n = 7, surgery followed by three LLLT exposures, 12, 36, and 60 h after surgery). For each group, a sham group (n = 21) underwent surgery without laser application. The animals in the laser groups received an infrared diode continuous laser exposure (AsGaAl, 780 nm wavelength, power of 20 mW, energy density of 10 J/cm(2), spot size of 0,04 cm(2)) on three points (20 s per point), and a final energy of 0.4 J. The animals were sacrificed 36 h (laser I and sham I groups), 60 h (laser II and sham II), and 84 h (laser III and sham III groups) after surgery. The MCP-1 concentrations were measured by cytometric bead array. There was no significant difference between the three periods in the sham group (p = 0.3). There was a lower concentration of MCP-1 in the laser III group compared to the laser I group (p = 0.05). The infrared LLLT showed a cumulative effect in the modulation of chemokine MCP-1 concentration. Three LLLT exposures were necessary to achieve the MCP-1 modulation.


Subject(s)
Chemokine CCL2/blood , Inflammation/radiotherapy , Low-Level Light Therapy/methods , Animals , Inflammation/metabolism , Infrared Rays , Lasers, Semiconductor/therapeutic use , Low-Level Light Therapy/instrumentation , Mice , Mice, Inbred BALB C , Skin/injuries , Skin/radiation effects
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