• Tue. Sep 27th, 2022

The treatment with TLR-agonists would help the host immune system subverting these anti-inflammatory cells to a pro-inflammatory profile, favoring the resolution of the infection


Sep 2, 2022

The treatment with TLR-agonists would help the host immune system subverting these anti-inflammatory cells to a pro-inflammatory profile, favoring the resolution of the infection. findings shed light on the CBM treatment, which might target neutrophil polarization as a new therapy approach to treat CBM lesions. is a dematiaceous fungus of the Herpotrichiellaceae family, known as the main agent of chromoblastomycosis (CBM) disease, a deep and chronic subcutaneous mycosis1,2. The CBM lesions are characterized by verrucous, erythematous papules, and atrophic lesions in the skin3. Similar to most fungal infections, the treatment of CBM is complex and usually demands multi-drug administration4 associated with heat/freezing therapy5,6 and, in some cases, surgery7. Moreover, costly and long-term treatments might result in high rates of disease relapse NRA-0160 and treatment discontinuation. Therefore, understanding the hostCpathogen interaction is crucial to develop new therapeutic tools for CBM treatment8. In the NRA-0160 last decade, great effort was made to understand the host immune response in CBM infection (for a review in this topic see Ref.8). Skin biopsies from CBM patients show a characteristic external layer of fibrous tissue NRA-0160 with an internal layer of thick granulomatous inflammatory tissue containing mainly macrophages and NRA-0160 neutrophils9C11. Several studies have demonstrated that the macrophage is poorly activated in CBM and does not seem to play a crucial role in this disease12C15. However, the importance of neutrophils controlling fungal spread remains unclear. One of the leading studies demonstrating the neutrophil fungicidal activity against conidia was published in the 1990s by the Rozental Rabbit Polyclonal to ACAD10 group16. Recently, our group demonstrated that neutrophils eliminate conidia in vitro through TLR-2 and TLR-4-dependent phagocytosis and ROS production, whereas hyphal killing occurs through Neutrophil Extracellular Traps (NETs) released independently of ROS production and TLR-2/TLR-4 receptors17. Neutrophilsalso named polymorphonuclear (PMN) cellsare granulocytes from the innate immune system, known to be essential in several fungal infections, including specific-antibody production. This pattern is usually observed in patients with mild disease, while lower T-cell response and greater antibody titers are associated with severe forms of the disease. Therefore, our results suggest that modulates neutrophils to an anti-inflammatory/PMN-MDSC profile with implications for host protection in the CBM infection. Material and methods Animals The experimental protocols involving animals were previously approved by the Institutional Ethics Committee for Animal Care and Research at the School of Pharmaceutical Sciences (CEUA/FCF Protocol 474). The in vivo experiments were carried out following the recommendations of the ARRIVE Guidelines and the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Briefly, male C57Bl/6 mice at 10C12?weeks of age were obtained from the Animal House Production and Experimentation Facility of the School of Pharmaceutical Sciences of the University of S?o Paulo. The animals were maintained in an SPF environment and housed in temperature-controlled rooms at 23C25?C with food and water ad-libitum throughout the experiments. The euthanasia procedure was performed according to the American Veterinary Medical Association Guidelines for the Euthanasia of Animals (2020), using the overdose of ketamine and xylazine method. In this study, we used 4C5 animals per group and we performed the experiments in two independent days. These NRA-0160 two experiments were compiled, unless otherwise stated. In this study, no strategies were used to blind or randomize our groups. Fungal strain and growth conditions This study was conducted using strain CBS 271.37, which was previously isolated from a Brazilian patient diagnosed with CBM. The genome of CBS 271.37 is completely sequenced and this strain is commonly used to study infection due.