Guanylate binding proteins contained in the murine chromosome 3 are important to control mycobacterial infection.

Guanylate binding proteins (GBPs) are important effector molecules of autonomous response induced by proinflammatory stimuli, mainly IFNs. The murine GBPs clustered in chromosome 3 (GBPchr3) contains the majority of human homologous GBPs. Despite intense efforts, mycobacterial-promoted diseases are still a major public health problem. However, the combined importance of GBPchr3 during mycobacterial infection has been overlooked. This study addresses the influence of the GBPchr3 in host immunity against mycobacterial infection to elucidate the relationship between cell-intrinsic immunity and triggering of an efficient anti-mycobacterial immune response. Here we show that all GBPchr3 are up-regulated in lungs of mice during Mycobacterium bovis BCG infection, resembling tissue expression of IFN-γ. Mice deficient in GBPchr3 (GBPchr3-/- ) were more susceptible to infection, displaying diminished expression of autophagy-related genes (LC3B, ULK1, and ATG5) in lungs. Additionally, there was reduced proinflammatory cytokine production complementary to diminished numbers of myeloid cells in spleens of GBPchr3-/- . Higher bacterial burden in GBPchr3-/- animals correlated with increased number of tissue granulomas. Furthermore, absence of GBPchr3 hampered activation and production of TNF-α and IL-12 by dendritic cells. Concerning macrophages, lack of GBPs impaired their antimicrobial function, diminishing autophagy induction and intracellular killing efficiency. In contrast, single GBP2 deficiency did not contribute to in vivo bacterial control. In conclusion, this study shows that GBPchr3 are important not only to stimulate cell-intrinsic immunity but also for inducing an efficient immune response to control mycobacterial infection in vivo.

Evaluation of the antimicrobial activity of the mastoparan Polybia-MPII isolated from venom of the social wasp Pseudopolybia vespiceps testacea (Vespidae, Hymenoptera).

Mastoparans, a class of peptides found in wasp venom, have significant effects following a sting as well as useful applications in clinical practice. Among these is their potential use in the control of micro-organisms that cause infectious diseases with a significant impact on society. Thus, the present study describes the isolation and identification of a mastoparan peptide from the venom of the social wasp Pseudopolybia vespiceps and evaluated its antimicrobial profile against bacteria (Staphylococcus aureus and Mycobacterium abscessus subsp. massiliense), fungi (Candida albicans and Cryptococcus neoformans) and in vivo S. aureus infection. The membrane pore-forming ability was also assessed. The mastoparan reduced in vitro and ex vivo mycobacterial growth by 80% at 12.5 µM in infected peritoneal macrophages but did not affect the shape of bacterial cells at the dose tested (6.25 µM). The peptide also showed potent action against S. aureus in vitro (EC50 and EC90 values of 1.83 µM and 2.90 µM, respectively) and reduced the in vivo bacterial load after 6 days of topical treatment (5 mg/kg). Antifungal activity was significant, with EC50 and EC90 values of 12.9 µM and 15.3 µM, respectively, for C. albicans, and 11 µM and 22.70 µM, respectively, for C. neoformans. Peptides are currently attracting interest for their potential in the design of antimicrobial drugs, particularly due to the difficulty of micro-organisms in developing resistance to them. In this respect, Polybia-MPII proved to be highly effective, with a lower haemolysis rate compared with peptides of the same family.

Influência do óleo de Copaifera langsdorffii no reparo de ferida cirúrgica em presença de corpo estranho / Influence of Copaifera langsdorffii oil on the repair of a surgical wound in the presence of foreign body

A Copaifera langsdorffii é uma leguminosa nativa do Brasil, da qual pode ser extraído um óleo, popularmente conhecido como óleo de copaíba. Este óleo é amplamente utilizado para tratamento de feridas cutâneas por ser reconhecido como antiinflamatório e cicatrizante. Apesar disso, poucas comprovações científicas do verdadeiro efeito terapêutico desta planta medicinal foram produzidas. O objetivo desse trabalho foi avaliar o efeito do tratamento tópico com C. langsdorffii no processo de reparo quando um corpo estranho é o indutor da inflamação. Para isso, 60 camundongos da linhagem BALB/c foram submetidos à incisão cirúrgica linear de 1cm no dorso para realizar o implante de uma lamínula de vidro com 12mm de diâmetro no tecido subcutâneo. Quatro tratamentos para a ferida foram estabelecidos: controle (C) tratado com solução salina estéril, controle veículo (CV) tratado com óleo mineral estéril, tratamento 1 (T1) tratado com diluição (v:v) de óleo mineral estéril e óleo de C. langsdorffii, tratamento 2 (T2) tratado com óleo de C. langsdorffii puro. As avaliações foram realizadas em períodos de tempo pré-determinados (1, 3, 5, 7 e 14 dias). Era possível perceber características da fase proliferativa como a reepitelização, a presença de fibroblastos e a neovascularização, porém os grupos tratados com o óleo (T1 e T2) não apresentavam reepitelização aos três dias. Esses grupos aos 5 e 7 dias apresentavam no exame macroscópico maior intensidade de edema, hiperemia e permanência de crostas. Na microscopia, a reepitelização ainda não estava completa e a crosta era serocelular. Nos grupos C e CV, apesar de discreta, era predominante a presença de mononucleares, enquanto nos grupos T1 e T2 o infiltrado inflamatório era misto e com maior intensidade que nos outros grupos. Quatorze dias depois da incisão cirúrgica, os aspectos macroscópicos dos grupos C e CV eram semelhantes e os grupos T1 e T2, apesar de a ferida estar completamente fechada e sem...

Copaifera langsdorffii is a Brazilian native leguminosae that produce resin-oil, popularly known as copaíba oil. This oil is used for the treatment of skin wound due to its recognized antiinflammatory and wound healing effects. Despite, its popular use, there are few published data about the therapeutic effect of this medicinal plant. The aim of the study was to evaluate the topic treatment effect of the Copaíba oil on the process of skin repair inflammation induced by a foreign body subcutanously implanted. Sixty BALB/c mice were submitted to a 1cm linear incision and a 12mm circle coverslip was subcutaneously implanted. Four treatments groups were established: control, sterile saline (C); vehicle control, sterile mineral oil, (VC); treatment 1 (T1), mineral oil plus copaiba oil (V/V), and treatment 2 (T2) copaiba oil. The evaluations were performed at pre-determined time points (1, 3, 5, 7 and 14 days). It was possible to find fibroblasts, epithelial cells proliferation, re-epithelization and newly formed blood vessels in all groups, however, all oil treated groups (T1 and T2) did not present re-epithelization at three days post surgical incision. On days 5 and 7, a higher intensity of edema and hyperemia on the groups T1 and T2 was observed, besides that, the T1 and T2 groups presented a serous cellular scab on the wounds that was absent on the C and VC groups. The inflammatory reactions among the groups C and VC showed more mononuclear cells than the T1 and T2 groups that presented a mixed cell patter composed from both mono and polymorphonuclear cells. Although the surgical wounds were re-epithelizaded, in the groups T1 and T2, they were covered by a serous cellular crust and the dermis tissue still presented an intense mononuclear cell inflammatory focus. Fourteen days after of the surgical incision, the gross aspects on groups C and VC were similar and on groups T1 and T2, despite wound to be completely closed and without...