Inflammatory effects of particulate matter air pollution Arias-Pérez, Rubén D.; Taborda, Natalia A.; Gómez, Diana M. ...
Environmental science and pollution research international,
12/2020, Letnik:
27, Številka:
34
Journal Article
Recenzirano
Air pollution is an important cause of non-communicable diseases globally with particulate matter (PM) as one of the main air pollutants. PM is composed of microscopic particles that contain a ...mixture of chemicals and biological elements that can be harmful to human health. The aerodynamic diameter of PM facilitates their deposition when inhaled. For instance, coarse PM having a diameter of < 10 μm is deposited mainly in the large conducting airways, but PM of < 2.5 μm can cross the alveolar-capillary barrier, traveling to other organs within the body. Epidemiological studies have shown the association between PM exposure and risk of disease, namely those of the respiratory system such as lung cancer, asthma, and chronic obstructive pulmonary disease (COPD). However, cardiovascular and neurological diseases have also been reported, including hypertension, atherosclerosis, acute myocardial infarction, stroke, loss of cognitive function, anxiety, and Parkinson’s and Alzheimer’s diseases. Inflammation is a common hallmark in the pathogenesis of many of these diseases associated with exposure to a variety of air pollutants, including PM. This review focuses on the main effects of PM on human health, with an emphasis on the role of inflammation.
Despite the suppression of viral replication induced by the highly active anti-retroviral therapy (HAART), an increased immune activation and inflammatory state persists in HIV-infected patients, ...contributing to lower treatment response and immune reconstitution, and development of non-AIDS conditions. The chronic activation and inflammation affect the functionality and differentiation of CD8+ T-cells, particularly reducing their cytotoxic capacity, which is critical in the control of HIV replication. Although previous studies have shown that HAART induce a partial immune reconstitution, its effect on CD8+ T-cells cytotoxic function, as well as its relationship with the inflammatory state, is yet to be defined. Here, we characterized the functional profile of polyclonal and HIV-specific CD8+ T cells, based on the expression of cell activation and differentiation markers, in individuals chronically infected with HIV, under HAART. Compared with seronegative controls, CD8+ T-cells from patients on HAART exhibited a low degranulation capacity (surface expression of CD107a), with consequent low secreted levels and high intracellular expression of granzyme B and perforin. This degranulation defect was particularly observed in those cells expressing the activation marker HLA-DR, which were further characterized as effector memory cells with high expression of CD57. The expression of CD107a, but not of granzyme B and perforin, in CD8+ T-cells from HIV-infected patients on HAART reached levels similar to those in seronegative controls when the treatment duration was higher than 25 months. In addition, the expression of CD107a was negatively correlated with the expression of exhaustion markers on CD8+ T-cells and the plasma inflammatory molecule sCD14. Thus, despite HAART-induced viral suppression, CD8+ T-cells from HIV-infected patients have an alteration in their cytotoxic program. This defect is associated with the cellular activation, differentiation and exhaustion state, as well as with the inflammation levels, and can be partially recovered with a long and continuous treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the combined antiretroviral therapy (cART) has decreased the deaths associated with the immune deficiency acquired syndrome (AIDS), non-AIDS conditions have emerged as an important cause of ...morbidity and mortality in HIV-infected patients under suppressive cART. Since these conditions are associated with a persistent inflammatory and immune activation state, major efforts are currently made to improve the immune reconstitution. CD8
T-cells are critical in the natural and cART-induced control of viral replication; however, CD8
T-cells are highly affected by the persistent immune activation and exhaustion state driven by the increased antigenic and inflammatory burden during HIV infection, inducing phenotypic and functional alterations, and hampering their antiviral response. Several CD8
T-cell subsets, such as interleukin-17-producing and follicular CXCR5
CD8
T-cells, could play a particular role during HIV infection by promoting the gut barrier integrity, and exerting viral control in lymphoid follicles, respectively. Here, we discuss the role of CD8
T-cells and some of their subpopulations during HIV infection in the context of cART-induced viral suppression, focusing on current challenges and alternatives for reaching complete reconstitution of CD8
T-cells antiviral function. We also address the potential usefulness of CD8
T-cell features to identify patients who will reach immune reconstitution or have a higher risk for developing non-AIDS conditions. Finally, we examine the therapeutic potential of CD8
T-cells for HIV cure strategies.
Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of ...curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre-post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre-post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.
The human immunodeficiency virus type 1 (HIV-1) reservoir, composed of cells harboring the latent, integrated virus, is not eliminated by antiretroviral therapy. It therefore represents a significant ...barrier to curing the infection. The biology of HIV-1 reservoirs, the mechanisms of their persistence, and effective strategies for their eradication are not entirely understood. Here, we review the molecular mechanisms by which HIV-1 reservoirs develop, the cells and compartments where the latent virus resides, and advancements in curative therapeutic strategies. We first introduce statistics and relevant data on HIV-1 infection, aspects of pathogenesis, the role of antiretroviral therapy, and the general features of the latent HIV reservoir. Then, the article is built on three main pillars: The molecular mechanisms related to latency, the different strategies for targeting the reservoir to obtain a cure, and the current progress in immunotherapy to counteract said reservoirs.
Graphical Abstract
Airborne particulate matter produced by industrial sources and automobiles has been linked to increased susceptibility to infectious diseases and it is known to be recognized by cells of the immune ...system. The molecular mechanisms and changes in gene expression profiles induced in immune cells by PM have not been fully mapped out or systematically integrated. Here, we use RNA-seq to analyze mRNA profiles of human peripheral blood mononuclear cells after exposure to coarse particulate matter (PM
). Our analyses showed that PM
was able to reprogram the expression of 1,196 genes in immune cells, including activation of a proinflammatory state with an increase in cytokines and chemokines. Activation of the IL-36 signaling pathway and upregulation of chemokines involved in neutrophil and monocyte recruitment suggest mechanisms for inflammation upon PM exposure, while NK cell-recruiting chemokines are repressed. PM exposure also increases transcription factors associated with inflammatory pathways (e.g., JUN, RELB, NFKB2, etc.) and reduces expression of RNases and pathogen response genes CAMP, DEFAs, AZU1, APOBEC3A and LYZ. Our analysis across gene regulatory and signaling pathways suggests that PM plays a role in the dysregulation of immune cell functions, relevant for antiviral responses and general host defense against pathogens.
Intestinal microbiota facilitates food breakdown for energy metabolism and influences the immune response, maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal ...dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression or if it could modulate the risk of acquiring the HIV infection. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha (p = 0.040) and beta diversity (p = 0.006) compared to HC, but no differences were found compared to HIV+. A lower Treg percentage was observed in HESN (1.77%) than HC (2.98%) and HIV+ (4.02%), with enrichment of the genus Butyrivibrio (p = 0.029) being characteristic of this profile. Moreover, we found that Megasphaera (p = 0.017) and Victivallis (p = 0.0029) also are enriched in the microbiota composition in HESN compared to HC and HIV+ subjects. Interestingly, an increase in Succinivibrio and Prevotella, and a reduction in Bacteroides genus, which is typical of HIV-infected individuals, were observed in both HESN and HIV+, compared to HC. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The epidemiological association between exposure to particulate matter (PM
) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these effects remain ...unclear. Neutrophils play an essential role in immune defense against foreign agents and also participate in the development of inflammatory responses. However, the role of these cells in the PM
induced inflammatory response is not yet fully established. Thus, this study aims to evaluate the effect of PM
on the neutrophil-mediated inflammatory response. For this, neutrophils from healthy adult human donors were in vitro exposed to different concentrations of PM
. The cell viability and cytotoxic activity were evaluated by MTT. LDH, propidium iodide and reactive oxygen species (ROS) were quantified by flow cytometry. Interleukin 8 (IL-8) expression, peptidyl arginine deiminase 4 (PAD
), myeloperoxidase (MPO), and neutrophil elastase (NE) expression were measured by RT-PCR. IL-8 was also quantified by ELISA. Fluorescence microscopy was used to evaluate neutrophil extracellular traps (NETs) release. The in vivo inflammatory responses were assessed in BALB/c mice exposed to PM
by histopathology and RT-PCR. The analysis shows that PM
exposure induced a cytotoxic effect on neutrophils, evidenced by necrosis and LDH release at high PM
concentrations. ROS production, IL-8, MPO, NE expression, and NETs release were increased at all PM
concentrations assessed. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF), histopathological changes with inflammatory cell infiltration, and CXCL1 expression were observed in PM
-treated mice. The results suggest that lung inflammation in response to PM
could be mediated by neutrophils activation. In this case, these cells migrate to the lungs and release pro-inflamatory mediators, including ROS, IL-8, and NETs. Thus, contributing to the exacerbation of respiratory pathologies, such as allergies, infectious and obstructive diseases.
Despite being under constant exposure to HIV-1, some individuals do not show serological or clinical evidence of infection and are known as HESN (HIV-Exposed Seronegative). Multiple studies in ...different HESN cohorts have linked the NK cells as a correlate of resistance; however, little is known about the role of these cells in Men Who Have Sex with Men (MSM) with high risk sexual behaviors. We evaluated a general overview of activation and effector features of NK cells of MSM co-cultured with LT CD4+ HIV+ in which MSM at high risk of HIV-1 infection (HR-MSM) exhibit higher capacity to eliminate infected cells, reduced percentages of CD69+ cells when compared to MSM at low risk of infection (LR-MSM). In addition, we found that, despite the lower levels of CD69+ NK cells on HR-MSM group, within this population, higher percentages of CD69+ IFN-γ+ and CD69+ NKG2D+ NK cells were found together with higher levels of RANTES and Granzyme B production with higher antiviral capacity, resulting in a lower concentration of p24 protein and p24+ CD4+ T cells. Altogether, this information suggests that NK cells of MSM could impact the capacity to face the viral infection.
BACKGROUND:Despite advances made with the highly active antiretroviral therapy (HAART) in the control of the HIV 1 infection, a cure has not been achieved because of the persistence of viral ...reservoirs. The major HIV reservoirs remain in the lymphoid follicles because of, among other factors, the partial absence of CD8 T-cells in these structures. Recently, lymphoid follicle–confined and circulating CD8 T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms that could help to control HIV replication.
SETTING AND METHODS:By flow cytometry, we characterized the phenotype and function of circulating CXCR5-expressing CD8 T-cells in HIV-infected patients with natural or HAART-induced control of HIV replication.
RESULTS:Circulating CXCR5-expressing CD8 T-cells exhibited low or null expression of the C–C chemokine receptor type 7 (CCR7) and had a transitional memory phenotype. Particular redistributions of CXCR5-expressing CD8 T-cells were found in HIV-infected patients, and they were partially restored by HAART. The frequency of CXCR5CCR7 CD8 T-cells was higher in spontaneous HIV controllers and negatively correlated with plasma HIV RNA levels. Total and HIV-specific CXCR5 CD8 T-cells were major producers of interleukin-21, and this function was positively associated with their interferon-γ production.
CONCLUSIONS:Circulating CXCR5-expressing CD8 T-cells are associated with low-level HIV replication; these cells could be novel correlates of protection, and potentially useful in the eradication of HIV reservoirs.
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