Photobiomodulation enhances the Th1 immune response of human monocytes.

This study aims to evaluate the effects of photobiomodulation (PBM) on human monocytes, assessing the oxidative burst and ultimate fungicidal potential of these cells, as well as the gene expression at the mRNA level of CD68, CD80, CD163, CD204, IL-6, TNF-α and IL-10 in derived macrophages. Primary cultures of human monocytes were irradiated with an InGaAlP (660 nm)/GaAlAs (780 nm) diode laser (parameters: 40 mW, 0.04 cm2, 1 W/cm2; doses: 200, 400 and 600 J/cm2). Cells were submitted to the chemiluminescence assay, and a microbicidal activity assay against Candida albicans was performed. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured, and cell viability was assessed by the exclusion method using 0.2% Trypan blue reagent. Irradiated monocytes were cultured for 72 h towards differentiation into macrophages. Total RNA was extracted, submitted to reverse transcription and real-time PCR. The results were analysed by ANOVA and the Tukey test (α = 0.05). Irradiated monocytes revealed a significant increase in their intracellular and extracellular ROS (P < 0.001). The 660 nm wavelength and 400 J/cm2 dose were the most relevant parameters (P < 0.001). The fungicidal capacity of the monocytes was shown to be greatly increased after PBM (P < 0.001). PBM increased the expression of TNF-α (P = 0.0302) and the production of NO (P < 0.05) and did not impair monocyte viability. PBM induces a pro-inflammatory Th1-driven response in monocytes and macrophages.

Epitope-Based Vaccine of a Brucella abortus Putative Small RNA Target Induces Protection and Less Tissue Damage in Mice.

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.

No effect of prior Dengue virus 1 infection in mouse dams on long-term behavioral profiles in offspring infected with Zika virus during gestation.

Zika virus (ZIKV) is a mosquito-borne Flavivirus structurally and antigenically related to Dengue virus (DENV). Zika virus has been associated with congenital anomalies and most ZIKV outbreaks have occurred in endemic areas of DENV. The present study investigated the effects of prior DENV serotype 1 (DENV1) immunity in immunocompetent female Swiss mice on gestational ZIKV infection in offspring. Physical/reflex development, locomotor activity, anxiety, visual acuity, and brain-derived neurotrophic factor (BDNF) levels were evaluated in offspring during infancy and adolescence. Anti-DENV1 and anti-ZIKV antibodies were detected in sera of the progenitors, whereas no ZIKV genomes were detected in the offspring brain. Pups from dams with only DENV1 immunity presented alterations of physical/reflex development. Pups from all infected dams exhibited time-related impairments in locomotor activity and anxiolytic-like behavior. Offspring from DENV/ZIKV-infected dams exhibited impairments in visual acuity during infancy but not during adolescence, which was consistent with morphometric analysis of the optic nerve. Pups from DENV1-, ZIKV-, and DENV/ZIKV-infected dams exhibited a decrease in BDNF levels during infancy and an increase during adolescence in distinct brain regions. In summary, we found no influence of prior DENV1 immunity on gestational ZIKV infection in offspring, with the exception of alterations of early visual parameters, and an increase in BDNF levels in the hippocampus during adolescence.

Vancomycin-induced gut dysbiosis during Pseudomonas aeruginosa pulmonary infection in a mice model.

Pseudomonas aeruginosa is one of the most common opportunistic pathogens causing respiratory infections in hospitals. Vancomycin, the antimicrobial agent usually used to treat bacterial nosocomial infections, is associated with gut dysbiosis. As a lung-gut immunologic axis has been described, this study aimed to evaluate both the immunologic and histopathologic effects on the lungs and the large intestine resulting from vancomycin-induced gut dysbiosis in the P. aeruginosa pneumonia murine model. Metagenomic analysis demonstrated that vancomycin-induced gut dysbiosis resulted in higher Proteobacteria and lower Bacteroidetes populations in feces. Given that gut dysbiosis could augment the proinflammatory status of the intestines leading to a variety of acute inflammatory diseases, bone marrow-derived macrophages were stimulated with cecal content from dysbiotic mice showing a higher expression of proinflammatory cytokines and lower expression of IL-10. Dysbiotic mice showed higher levels of viable bacteria in the lungs and spleen when acutely infected with P. aeruginosa, with more lung and cecal damage and increased IL-10 expression in bronchoalveolar lavage. The susceptible and tissue damage phenotype was reversed when dysbiotic mice received fecal microbiota transplantation. In spite of higher recruitment of CD11b+ cells in the lungs, there was no higher CD80+ expression, DC+ cell amounts or proinflammatory cytokine expression. Taken together, our results indicate that the bacterial community found in vancomycin-induced dysbiosis dysregulates the gut inflammatory status, influencing the lung-gut immunologic axis to favor increased opportunistic infections, for example, by P. aeruginosa.

Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions.

The gastrointestinal tract has become a focus of study recently. The crosstalk between microbiota, especially bacteria, and the intestinal mucosa has to be accurately balanced in order to maintain physiological homeostasis in the human body. This dynamic interaction results in different levels of short-chain fatty acids (SCFAs), IgA, and T cell lymphocyte subsets, which could lead the human body towards health or disease. The disruption of this microbiome characterises gut dysbiosis. Antibiotics are usually prescribed to fight against bacterial infection. They can also modulate the human microbiome, since it acts directly over organisational taxonomic units (OTUs) when taken orally. As a result, these pharmaceuticals enable gut dysbiosis and its systemic effects due to microbiome disturbance. Here, current data have been gathered from mice model experiments and epidemiological studies in an antibiotic-centred perspective. The presented data suggest the importance of translational studies in a murine model focusing on GIT homeostasis with bacterial groups since any changes to the GIT-microbiota have systemic repercussions in human health and disease.