Baker, C. P.; Laba, S.; Warner, J.; Shepherd, K.; Wilson, H. M.; Arthur, J. S. C.

Candida albicans is a commensal fungus which populates most healthy individuals microbiota but can turn opportunistic in immunocompromised individuals and cause severe disease linked with high rates of mortality. With limited therapeutic options and increasing resistance to antifungals, novel treatment strategies for C. albicans infections is paramount. The exact immune response to C. albicans infections can be influenced by the surrounding microenvironment, for example, metabolic stresses or co-infection; although, knowledge on whether responses are enhanced or inhibited is lacking. Macrophages are a key immune cell in defence against C. albicans infection through phagocytic uptake and cytokine production that alerts other immune defence mechanisms. Here, we utilise a discovery screen approach using Data Independent Acquisition (DIA) based total proteomics to describe 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 live 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 the BMDM proteome landscape and selectively suppressed BMDM secreted IL-6 and IL-12p40 cytokine responses to P. aeruginosa. Thus, C. albicans has significant suppressive capabilities in the host innate immune responses that could impact clinical outcomes during infection.