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When macrophages from patients with cryopyrin-associated autoinflammatory syndrome are treated with -(1,3)-glucan, they have reduced caspase-1 activation and IL-1 release compared with untreated macrophages [[71]], which could be therapeutically beneficial for these patients. Candida albicans Molecular mechanisms of inflammasome regulation In vitro, I C. albicans i induces caspase-1 cleavage and IL-1 release in an NLRP3- and caspase-1- dependent manner in macrophages and dendritic cells (DCs) (Fig 1A) [[16]-[19]]. Initial studies focused on the role of the IL-1 family cytokines IL-1 and IL-1 in restricting the fungal pathogen I C i . The CLR pathway is activated via the adaptor protein SYK, and the downstream supramolecular complex CARD9-Bcl-10-MALT1 drives the recruitment of caspase-8/ASC and/or NLRP3/ASC/caspase-1 to cleave gasdermin D and process and release IL-1 . [Extracted from the article]

Innate immunity responds to pathogens by producing alarm signals and activating pathways that make host cells inhospitable for pathogen replication. The intracellular bacterium Burkholderia thailandensis invades the cytosol, hijacks host actin, and induces cell fusion to spread to adjacent cells, forming multinucleated giant cells (MNGCs) which promote bacterial replication. We show that type I interferon (IFN) restricts macrophage MNGC formation during B. thailandensis infection. Guanylate-binding proteins (GBPs) expressed downstream of type I IFN were required to restrict MNGC formation through inhibition of bacterial Arp2/3-dependent actin motility during infection. GTPase activity and the CAAX prenylation domain were required for GBP2 recruitment to B. thailandensis, which restricted bacterial actin polymerization required for MNGC formation. Consistent with the effects in in vitro macrophages, Gbp2−/−, Gbp5−/−, GbpChr3-KO mice were more susceptible to intranasal infection with B. thailandensis than wildtype mice. Our findings reveal that IFN and GBPs play a critical role in restricting cell-cell fusion and bacteria-induced pathology during infection. Author summary: The intracellular bacterium Burkholderia thailandensis and its relatives B. pseudomallei and B. mallei each invade host cells and hijack the actin cytoskeleton polymerization machinery to transmit to neighboring cells by cell-cell fusion, a transmission strategy that is unique to this family. The high antibiotic resistance of the Burkholderia family underscores the need to understand how the immune system can control infections. Here, we show that the interferon immune response upregulates a family of immune proteins, the guanylate binding proteins (GBPs), to counter the bacterial intracellular motility and, as a consequence, cell-cell fusion. Infected macrophages extensively fuse when lacking key molecules in this immune pathway, and mice lacking the GBP2 or GBP5 proteins are 100-1000-fold more susceptible to infection than wildtype mice, highlighting the critical role this immune pathway plays in restricting bacterial infection and cell-cell fusion. We also found that mice lacking GBPs were protected if bacteria lacked a critical virulence factor, VgrG5, that is required for cell-cell fusion, highlighting that cell-cell fusion is dependent on both bacteria-mediated cytoskeleton remodeling as well as VgrG5. Together, this study provides insight into an intricate host-pathogen interaction key to the virulence of the Burkholderia family. [ABSTRACT FROM AUTHOR]

Background: Biofilms are communal structures of microorganisms that have long been associated with a variety of persistent infections poorly responding to conventional antibiotic or antifungal therapy. Aspergillus fumigatus fungus and Stenotrophomonas maltophilia bacteria are examples of the microorganisms that can coexist to form a biofilm especially in the respiratory tract of immunocompromised patients or cystic fibrosis patients. The aim of the present study was to develop and assess an in vitro model of a mixed biofilm associating S. maltophilia and A. fumigatus by using analytical and quantitative approaches. Materials and Methods: An A. fumigatus strain (ATCC 13073) expressing a Green Fluorescent Protein (GFP) and an S. maltophilia strain (ATCC 13637) were used. Fungal and bacterial inocula (105 conidia/mL and 106 cells/mL, respectively) were simultaneously deposited to initiate the development of an in vitro mixed biofilm on polystyrene supports at 37°C for 24 h. The structure of the biofilm was analysed via qualitative microscopic techniques like scanning electron and transmission electron microscopy, and fluorescence microscopy, and by quantitative techniques including qPCR and crystal violet staining. Results: Analytic methods revealed typical structures of biofilm with production of an extracellular matrix (ECM) enclosing fungal hyphae and bacteria. Quantitative methods showed a decrease of A. fumigatus growth and ECM production in the mixed biofilm with antibiosis effect of the bacteria on the fungi seen as abortive hyphae, limited hyphal growth, fewer conidia, and thicker fungal cell walls. Conclusion: For the first time, a mixed A. fumigatus—S. maltophilia biofilm was validated by various analytical and quantitative approaches and the bacterial antibiosis effect on the fungus was demonstrated. The mixed biofilm model is an interesting experimentation field to evaluate efficiency of antimicrobial agents and to analyse the interactions between the biofilm and the airways epithelium. [ABSTRACT FROM AUTHOR]