RESUMEN
The removal of dead cells (efferocytosis) contributes to the resolution of the infection and preservation of the tissue. Depending on the environment milieu, macrophages may show inflammatory (M1) or anti-inflammatory (M2) phenotypes. Inflammatory leukocytes are recruited during infection, followed by the accumulation of infected and non-infected apoptotic cells (AC). Efferocytosis of non-infected AC promotes TGF-ß, IL-10, and PGE2 production and the polarization of anti-inflammatory macrophages. These M2 macrophages acquire an efficient ability to remove apoptotic cells that are involved in tissue repair and resolution of inflammation. On the other hand, the impact of efferocytosis of infected apoptotic cells on macrophage activation profile remains unknown. Here, we are showing that the efferocytosis of gram-positive Streptococcus pneumoniae-AC (Sp-AC) or gram-negative Klebsiella pneumoniae-AC (Kp-AC) promotes distinct gene expression and cytokine signature in macrophages. Whereas the efferocytosis of Kp-AC triggered a predominant M1 phenotype in vitro and in vivo, the efferocytosis of Sp-AC promoted a mixed M1/M2 activation in vitro and in vivo in a model of allergic asthma. Together, these findings suggest that the nature of the pathogen and antigen load into AC may have different impacts on inducing macrophage polarization.
Asunto(s)
Apoptosis , Fagocitosis , Macrófagos/metabolismo , Fenotipo , AntiinflamatoriosRESUMEN
Excessive use of medications, including the antiparasitic drug ivermectin, can lead to bacterial gut dysbiosis, an imbalance in the intestinal microbiome, which in turn may increase or decrease susceptibility to infectious processes. To better understand the effects of continuous ivermectin usage on the gut bacterial community, C57BL/6 isogenic mice were treated by gavage with ivermectin or saline. Ivermectin-induced bacterial gut dysbiosis is characterized by a decrease in Bacteroidetes, Firmicutes, Proteobacteria and Tenericutes and an increase in species of the phylum Verrucomicrobia. A pro-inflammatory immunostimulatory caecal content, as well as disruption of caecal tissue organization and liver tissue damage, was observed in mice with gut dysbiosis. However, ivermectin-induced gut dysbiosis did not lead to acute susceptibility to Pseudomonas aeruginosa lung infection: infected mice with and without gut dysbiosis showed similar rates of recovery of viable bacteria in organs, histopathology and differential cytokine expression in the lung. Therefore, an extension of liver damage was observed in ivermectin-treated and P. aeruginosa-infected mice, which was exacerbated by infection.
Asunto(s)
Ivermectina , Pseudomonas aeruginosa , Animales , Ratones , Ivermectina/efectos adversos , Disbiosis/inducido químicamente , Disbiosis/microbiología , Ratones Endogámicos C57BL , Pulmón , HígadoRESUMEN
Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and animals. Currently available live attenuated vaccines against brucellosis still have drawbacks. Therefore, subunit vaccines, produced using epitope-based antigens, have the advantage of being safe, cost-effective and efficacious. Here, we identified B. abortus small RNAs expressed during early infection with bone marrow-derived macrophages (BMDMs) and an apolipoprotein N-acyltransferase (Int) was identified as the putative target of the greatest expressed small RNA. Decreased expression of Int was observed during BMDM infection and the protein sequence was evaluated to rationally select a putative immunogenic epitope by immunoinformatic, which was explored as a vaccinal candidate. C57BL/6 mice were immunized and challenged with B. abortus, showing lower recovery in the number of viable bacteria in the liver, spleen, and axillary lymph node and greater production of IgG and fractions when compared to non-vaccinated mice. The vaccinated and infected mice showed the increased expression of TNF-α, IFN-γ, and IL-6 following expression of the anti-inflammatory genes IL-10 and TGF-ß in the liver, justifying the reduction in the number and size of the observed granulomas. BMDMs stimulated with splenocyte supernatants from vaccinated and infected mice increase the CD86+ marker, as well as expressing greater amounts of iNOS and the consequent increase in NO production, suggesting an increase in the phagocytic and microbicidal capacity of these cells to eliminate the bacteria.
Asunto(s)
Zoonosis Bacterianas/prevención & control , Vacuna contra la Brucelosis/inmunología , Brucella abortus/inmunología , Brucelosis/prevención & control , Aciltransferasas/genética , Animales , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Zoonosis Bacterianas/inmunología , Zoonosis Bacterianas/microbiología , Vacuna contra la Brucelosis/administración & dosificación , Vacuna contra la Brucelosis/genética , Brucella abortus/genética , Brucelosis/inmunología , Brucelosis/microbiología , Simulación por Computador , Modelos Animales de Enfermedad , Mapeo Epitopo/métodos , Humanos , Inmunogenicidad Vacunal , Macrófagos/inmunología , Macrófagos/microbiología , Ratones , Cultivo Primario de Células , ARN Bacteriano/genética , ARN Bacteriano/aislamiento & purificación , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunologíaRESUMEN
INTRODUCTION: Chronic pain is common in individuals with severe and moderate haemophilia who did not receive prophylaxis during childhood. OBJECTIVE: To verify the effectiveness of acupuncture in reducing intensity in chronic pain, changes in quality of life, joint function and impact on treatment satisfaction of haemophilia patients. METHODS: Single-blinded randomized clinical trial with 28 participants divided into two groups: Acupuncture (G1) treated with traditional unilateral acupuncture (side of greatest referred pain) and Control (G2) treated with transcutaneous electrical nerve stimulation (TENS), with electrodes on the joint of most intense pain. Both groups had a 20-minute session per week, total of 05 consecutive sessions. Before starting treatment, participants underwent sociodemographic assessment, physical assessment (HJHS), quality of life questionnaire (Haem-a-Qol) and treatment expectation (Likert scale). After the end of the fifth session, Haem-a-Qol, HJHS and degree of satisfaction (Likert) were performed. The assessment of pain intensity using the visual analogue scale (VAS) was performed before the beginning and after the end of all sessions in both groups. Statistical analysis was performed using ANOVA, Bonferroni, t test and chi-square test (P < .05). RESULTS: There was a statistical difference within and between groups G1 and G2 in reduction of VAS. In Haem-a-Qol, the groups showed similarity in quality of life. Both groups had high expectations for treatment. G1 presented a better degree of treatment satisfaction than G2. Total HJHS showed no difference within and between groups. CONCLUSION: Acupuncture was effective in reducing pain intensity in haemophilia patients with chronic joint disease when compared to TENS.