Regulatory T cells (Tregs) play an important role by controlling allergic inflammation of airways. Recently, it has been shown that statins have immunomodulatory properties, probably mediated by their effects on Tregs. Therefore, we evaluated the in vivo effect of atorvastatin (ATV) on Tregs and its association with the inflammatory process in a model of allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with intranasal OVA. ATV (40 mg/kg) was delivered by daily intraperitoneal injection for 7 or 15 days before each OVA challenge. ATV treatment for 7 days increased the frequency of Tregs in mediastinal lymph nodes (MLN) and the interleukin (IL)-10 in lungs. After 15 days of treatment, ATV increased the percentage of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+) and programmed cell death protein 1 (PD-1+) Tregs in the lung, without enhancing their suppressive activity, but also increased the percentage of conventional T cells expressing GITR+, PD1+, and OX-40 (tumor necrosis factor receptor superfamily member 4). Although no significant changes were observed in the number of inflammatory cells in the bronchoalveolar lavage (BAL), OVA-specific immunoglobulin E in the serum, and type 2 helper (Th2) cytokines in the lungs, there was a significant decrease of peribronchial inflammation that negatively correlated with the Tregs in MLN and the concentration of IL-10 in the lung. These results suggest that ATV has an immunomodulatory role possibly mediated by their effects on Tregs, which could contribute to the control of inflammation during allergic asthma. Further studies are necessary to elucidate the contribution of Treg to immunomodulatory action of statins in the context of allergic asthma.
Introduction: The HIV-exposed seronegative (HESN) status is for individuals who remain seronegative despite repeated exposure to HIV. One of the main cohorts within this group is men who have sex with men (MSM). Studies of this cohort have revealed different immunological and genetic mechanisms that can explain the phenomenon of natural HIV resistance. NK cells' higher effector capacity is related to natural resistance to HIV. Besides, a new population of NK cells with adaptive features was described recently. These cells are increased in some HESN cohorts and appear to be involved in better control of viral replication in primarily HIV-infected subjects. The present study evaluated the role of NK cells in the natural resistance to HIV-1 infection in MSM. Methodology: Phenotypic and functional features were evaluated in NK cells from two groups of MSM, at different risks of HIV infection, according to the number of sexual partners. The production of IFN-γ and β-chemokines was included in the analysis, as well as the cytotoxic capacity and adaptive NK cell frequency. Genetic features, such as HLA and KIR allele frequencies, were also explored. Results: High-risk MSM exhibit an increased frequency of fully mature and CD57 + /NKG2C high NK cells. These individuals also show higher cytotoxic capacity and IFN-γ production in response to K562 stimuli. NK cells with a CD107a + /IFN-γ + functional profile were found more frequently and displayed higher IFN-γ production capacity among high-risk MSM than among low-risk MSM. The protective allele HLA-B * 18 was only present in the high-risk MSM group as well as HLA-B * 39. The protective phenotype KIR3DL1/S1-HLA-B * Bw4, in a homozygous state, was particularly abundant in the high-risk population. Notably, some of these functional features were related to higher frequencies of mature and CD57 + /NKG2C high NK cells, which, in turn, were associated with a higher number of sexual partners. Conclusion: The changes observed in the NK cell compartment can be driven by the magnitude of sexual exposure and immunological challenges of high-risk individuals, which could influence their resistance/susceptibility to HIV infection.
HIV infection still represents a major public health problem worldwide, and a vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection and opens doors for new preventive and therapeutic strategies. Among HESN groups there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for the study of HESN because of their major exposure to HIV in the absence of infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. Sixty MSM at high-risk (n=16) and low-risk (n=44) of HIV-1 acquisition were included. No sex worker nor homozygous delta 32 mutation subjects were included. All the participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. The high-risk MSM presented a higher frequency of sexual partners in the last 3 months previous to the enrollment in the study (Median 30 vs. 2), lifetime sexual partners (Median 1708 vs. 26), and unprotected anal intercourse (Median 12.5 vs. 2) than low-risk MSM. This group also showed a quiescent profile of T cells and NK cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR-CD38+, CD4+Ki67+ T cells, NKG2D+ NK cells (CD3-CD16+CD56+), a significantly higher percentage of CD4+HLADR-CD38- and a tendency to show a higher percentage of CD8+HLADR+CD38- T cells, than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this cohort of MSM could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells, and increased expression of Serpin A1. It is necessary to continue the study of MSM at high-risk of exposure to HIV-1 to better understand the natural resistance to HIV.
Human immunodeficiency virus (HIV) infection still represents a major public health problem worldwide, and its vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection, and opens doors for new preventive and therapeutic strategies. Among HESN groups, there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for HESN study because of their major HIV exposure without infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. This study included 60 MSM at high-risk (n = 16) and low-risk (n = 44) of HIV-1 acquisition. No sex worker nor homozygous delta 32 mutation subjects were included. All participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. A higher frequency of sexual partners in the last 3 months before the study participation (median, 30 vs. 2), lifetime sexual partners (median, 1,708 vs. 26), and unprotected anal intercourse (median 12.5 vs. 2) was determined in high-risk MSM than low-risk MSM. High-risk MSM also showed a quiescent profile of T cells and natural killer (NK) cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR−CD38+, CD4+Ki67+ T cells, and NKG2D+ NK cells (CD3−CD16+CD56+), a significantly higher percentage of CD4+HLADR−CD38−, and a tendency to show a higher percentage of CD8+HLADR+CD38− T cells than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this MSM cohort could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells and an increased Serpin A1 expression. Further study on MSM at high risk of exposure to HIV-1 is necessary to better understand the natural resistance to HIV.
Introducción: la malaria gestacional afecta a las madres y al embrión o feto en desarrollo; requiere diagnóstico rápido y tratamiento oportuno y efectivo para evitar las complicaciones y muertes. Objetivo: comparar las técnicas de gota gruesa, PCR anidada y PCR en tiempo real (qRT-PCR), para diagnosticar infecciones submicroscópicas por Plasmodium falciparum y P. vivax.Metodología: se estudiaron 21 mujeres con manifestaciones clínicas de malaria, incluyendo gestantes y no gestantes, en Puerto Libertador, Córdoba, Colombia; de todas se obtuvieron muestras de sangre periférica y, en las gestantes, de placenta y cordón umbilical. Se extrajo el ADN y se lo amplificó por PCR anidada y cuantitativa (qRT-PCR). Para el análisis estadístico se usaron los programas Graphpad PRISM y EPIDAT.Resultados: las tres técnicas diagnosticaron satisfactoriamente la presencia de P. falciparum y P. vivax en sangre periférica, cordón y placenta. Las pruebas moleculares presentaron sensibilidad y especificidad del 100%; dos casos de infección por P. falciparum no identificados por gota gruesa (submicroscópicos) se diagnosticaron con las dos técnicas de PCR.Conclusión: la qRT-PCR es ventajosa en comparación con la PCR anidada porque su estandarización es más corta, requiere menos infraestructura y permite cuantificar el ADN.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.