Candida albicans infection suppresses lipopolysaccharide or Pseudomonas aeruginosa stimulated murine bone marrow derived macrophage (BMDM) responses

Candida albicans is an opportunistic human pathogen, that commonly causes localised infection of mucosal surfaces. Candida can also cause systemic infections, which remain difficult to treat and have a high risk of mortality. The immune response to C. albicans infection is complex and can be influenced by the surrounding microenvironment, for example, metabolic stresses or co-infection. Macrophages are a key immune cell in defence against C. albicans infection through phagocytosis of C. albicans and cytokine production to co-ordinate immune responses. Here, we utilise Data Independent Acquisition (DIA) based total proteomics to describe the murine bone marrow derived macrophage (BMDM) response to C. albicans infection as well as in response to co-infection with gram-negative bacterial outer membrane component lipopolysaccharide (LPS) or the gram-negative bacteria Pseudomonas aeruginosa. We found C. albicans induced a surprisingly muted immune response in BMDMs as compared to LPS or P. aeruginosa. Moreover, upon co-infection with LPS or P. aeruginosa, C. albicans suppressed P. aeruginosa and LPS induced IL-6 and IL-12p40 secretion as well as dampening proteomic remodelling in the macrophage in response to these agents. Thus, C. albicans has significant suppressive capabilities in the host innate immune responses that could impact clinical outcomes during infection.