Candida albicans facilitates Porphyromonas gingivalis phagocytosis and combined exposure stimulates predominantly M1 response in macrophages in vitro

Porphyromonas gingivalis has been associated with diseases such as atherosclerosis and Alzheimer's Disease and found in affected tissue, suggesting they can pass from the oral cavity into the bloodstream while evading the immune system. A possible mechanism is via interaction with Candida albicans that facilitates P. gingivalis survival and virulence in aerobic conditions and attracts macrophages, which could be a carrier for the pathogen to distant organs. The aim was to study the macrophage response upon exposure by P. gingivalis and C. albicans. Chemotaxis towards either P. gingivalis or C. albicans and association with P. gingivalis by macrophages was studied using time-lapse microscopy. Macrophages were exposed to both microorganisms to determine expression of pro-inflammatory M1 or anti-inflammatory M2 cytokines and genes using a cytokine bead array and qPCR. The results showed that macrophages were attracted towards C. albicans, not P. gingivalis. Both M1 and M2 macrophages could take up P. gingivalis from the hyphae of C. albicans. Exposure to both microorganisms led to polarization towards M1, as shown by a higher IL-6, IL-1β and TNFα release and lower expression of CD206 and CD209. In conclusion, C. albicans attracts macrophages to associate with P. gingivalis from the hyphae. A combined exposure predominantly triggers a pro-inflammatory response. By attracting macrophages and stimulating their immune response, C. albicans could facilitate phagocytosis of P. gingivalis by macrophages. P. gingivalis could use this to enter the body.