Carvalho, C. R. | bioRxiv Science

bioRxiv2024

Systemic effects of oral tolerance improve the healing of several and concomitant wounds in different body parts

Throughout our lives, we are continually subjected to different situations that can result in several and concomitant wounds to different parts of our body. The healing of these wounds is essential to maintaining health. Inflammation is an important step in wound healing, but in cases of intense or prolonged inflammation, pathological scarring or non-closure of the wound may occur. Assuming that leukocytes participate in wound healing and that it is possible to intervene systemically with inflammation, we investigated a way to promote better repair of multiple wounds that may occur at the same time. Oral tolerance is an immunological phenomenon that result from protein intake and that have systemic effects on inflammation. Previous works have shown that parenteral injection of tolerated proteins reduces the inflammatory infiltrate and improves skin wound healing. Herein we tested whether the injection of tolerated proteins improves the healing of several wounds in different body parts, such as on the skin of the back and in the external ear (the auricle). To induce oral tolerance to ovalbumin (OVA), eight weeks old C57BL/6 mice drank egg white diluted 1:5 in water for 3 consecutive days. Control mice drank water. Seven days after oral treatment, mice were submitted to excisional injuries in the skin of the back (6 mm) and in the ears (4 mm). Minutes before the injuries, the mice received an intraperitoneal injection of OVA + Al(OH)3. Seven and 40 days after injuries, tissue samples were collected and processed for histological analysis of the wounds. The results show that the injection of OVA in animals that drank OVA reduced the inflammatory infiltrate in all lesions. Besides, injection of OVA in animals that drank OVA promoted better organization of the extracellular matrix, with thicker and intertwined collagen fibers in the neodermis, resulting in smaller scars in the skin. Furthermore, the healing area of the ears of OVA-tolerant animals showed chondrocyte aggregates and less obvious fibrous scar tissue compared with control animals. In conclusion, systemic effects of oral tolerance positively influenced the healing of several lesions in different body parts.

immunology↗

bioRxiv2021

Resource sharing by outer membrane vesicles from a citrus pathogen

The causative agent of citrus canker disease, Xanthomonas citri pv. citri, was found to produce copious amounts of outer membrane vesicles (OMVs), frequently forming long membranous tubes under different culture conditions. Lipidomic analysis revealed significant differences in lipid composition between purified vesicles in relation to whole cells. The results suggest an enrichment in saturated cardiolipins and a decrease in unsaturated lipids in the OMV samples, possibly granting them a more rigid structure while allowing their high degree of curvature caused by their small diameters. The vesicles proteome was found to be significantly enriched in TonB-dependent receptors related to the acquisition of different nutrients. These proteins are known to transport siderophores, which were evidenced to be present in purified X. citri OMVs, along with essential metals including iron, zinc, and manganese quantified by elemental analysis. The availability of vesicle-associated nutrients to be incorporated by cells was demonstrated by the use of OMVs as the sole carbon source for bacterial growth. At last, the vesicles also presented esterase and protease activities, which have been associated with virulence in phytopathogens. These evidences point that X. citri cells can use OMVs to share resources within microbial communities, which has potential implications for microbial interactions and plant colonization, affecting their survival and persistence on the host and in the environment. ImportanceThe shedding of outer membrane vesicles appears to be universal in Gram-negative bacteria and effectively constitutes a unique secretion pathway for diverse molecules and proteins. To study their possible functions in the citrus pathogen Xanthomonas citri, purified vesicles from this bacterium were studied by omics and functional approaches. Nutrient transporters were found associated to these structures, which were evidenced to contain siderophores and essential metals. The availability of these nutrients to be incorporated by cells was then demonstrated by showing that purified vesicles can be used as sole carbon sources for microbial growth. Additionally, the samples also presented esterase and protease activities which can contribute to the release of substrates from plant host tissues. These observations help to establish the developing idea of vesicles as shared bacterial resources which can participate in shaping host-associated microbial communities in contrast to other interactions such as bacterial competition.

microbiology↗