Figure 3.

Respiratory tract biofilm infection models and proposed ABPs modes’ of action. Respiratory tract biofilm infection models can be obtained by the incorporation of the bacteria in agar or alginate, which is instilled intratracheally, or a solution containing the biofilm-forming bacteria, which are inoculated directly into the animals’ nostrils or by inhalation. These models simulate a process similar to cystic fibrosis. In this process, both the innate and adaptive immune systems promote an exacerbated response mediated by immune cells (e.g., neutrophil, macrophage, dendritic cell, and lymphocytes), cytokines (e.g., IFN-γ, TNF-α, IL-4, IL-6, IL-17, and IL-10), and chemokines (e.g., CXCL-1 and CXCL-2). Therefore, ABPs have been used as immunomodulators. Some ABPs regulate the migration of inflammatory cells, including neutrophils, also acting by modulating the cytokine-mediated inflammatory response and reducing pro-inflammatory cytokines (e.g., IL-6 and TNF-α, IL-1β). These activities may be associated with both increased survival after treatment with ABPs and reduced lung tissue damage in treated animals. Additionally, these peptides demonstrate potent antibacterial activity (alone or in synergism with antibiotics) and antibiofilm, along with LPS neutralization. All figures were made by the authors with a subscription version of BioRender.com.