Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to moisture‐damaged buildings

Indoor exposure to microbes and their structural and metabolic compounds is notoriously complex. To study proinflammatory interactions between the multiple microbial agents, macrophages derived from human THP‐1 monocytic cells were exposed to several concentrations of microbial toxins alone (emodin, enniatin B, physcion, sterigmatocystin, valinomycin) and in combination with microbial structural components (bacterial lipopolysaccharide [LPS] or fungal β‐glucan). While the expression of proinflammatory cytokines TNFα and IL‐1β to single toxins alone was modest, low‐dose co‐exposure with structural components increased the responses of emodin, enniatin B, and valinomycin synergistically, both at the mRNA and protein level, as measured by RT‐qPCR and ELISA, respectively. Co‐exposure of toxins and β‐glucan resulted in consistent synergistically increased expression of several inflammation‐related genes, while some of the responses with LPS were also inhibitory. Co‐exposure of toxins with either β‐glucan or LPS induced also mitochondrial damage and autophagocytosis. The results demonstrate that microbial toxins together with bacterial and fungal structural components characteristic to moisture‐damaged buildings can have drastic synergistic proinflammatory interactions at low exposure levels.