Different bacterial cargo in apoptotic cells drive distinct macrophage phenotypes.

The removal of dead cells (efferocytosis) contributes to the resolution of the infection and preservation of the tissue. Depending on the environment milieu, macrophages may show inflammatory (M1) or anti-inflammatory (M2) phenotypes. Inflammatory leukocytes are recruited during infection, followed by the accumulation of infected and non-infected apoptotic cells (AC). Efferocytosis of non-infected AC promotes TGF-ß, IL-10, and PGE2 production and the polarization of anti-inflammatory macrophages. These M2 macrophages acquire an efficient ability to remove apoptotic cells that are involved in tissue repair and resolution of inflammation. On the other hand, the impact of efferocytosis of infected apoptotic cells on macrophage activation profile remains unknown. Here, we are showing that the efferocytosis of gram-positive Streptococcus pneumoniae-AC (Sp-AC) or gram-negative Klebsiella pneumoniae-AC (Kp-AC) promotes distinct gene expression and cytokine signature in macrophages. Whereas the efferocytosis of Kp-AC triggered a predominant M1 phenotype in vitro and in vivo, the efferocytosis of Sp-AC promoted a mixed M1/M2 activation in vitro and in vivo in a model of allergic asthma. Together, these findings suggest that the nature of the pathogen and antigen load into AC may have different impacts on inducing macrophage polarization.

Exploring how structural changes to new Licarin A derivatives effects their bioactive properties against rapid growing mycobacteria and biofilm formation.

Several species of rapidly growing mycobacteria (RGM) have been associated with biofilms in areas such as biomedical devices, water distribution systems, cosmetic surgery, and catheter-related blood infections. Biofilms which exhibit antimicrobial resistance such as those formed by the genus Mycobacterium pose a significant risk to health and are of particular interest to researchers. Licarin A (a neolignan found in numerous plant species e.g. nutmeg) has been reported to show a wide range of biological actions including anti-inflammatory, antioxidant, and antibacterial properties. The aim of this study was to prepare a set of Licarin A derivatives and investigate the impact of specific structural changes on its antimycobacterial ability, and its effect on the biofilm formation of RGM species. Initially, the phenolic sub-unit and alkenyl side chain of Licarin A were modified to create derivatives with a higher partition coefficient; as the activity of a compound against mycobacteria seems to be strongly influenced by its hydrophobicity. Further, polar groups were inserted into the side chain to change the hydrophilic-lipophilic profile of the molecules. Results showed variability in the susceptibility profile of mycobacteria against the Licarin A derivatives under analysis. A number of the derivatives showed significant inhibitory activity of planktonic growth of the three strains of mycobacteria used, with even lower MIC values than those observed with reference drugs and Licarin A itself. Cytotoxicity assays showed they also have low toxicity, confirming that structural modifications to the Licarin A have made improvements to its antimycobacterial properties.