Abstract
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.
Data availability
Mass spectrometry data has been deposited in PRIDE , under accession number PXD062689. Full scans of immunoblots are available in the supplementary data. Other data is available on request from the corresponding author.
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Acknowledgements
The authors would like to thank A. Brenes and A. Howden for proteomic analysis advice; Dundee University Biological Resource unit; A. Score, A. Atrih and the Fingerprint Proteomics Facility.
Funding
This work was funded by the Wellcome Trust (102132/B/13/Z) and EastBio (BBSRC BBSRC DTP Research BB/M010996/1) PhD Studentships.
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Conceptualization, JSCA, CPB, SL; methodology, JSCA, CPB, SL, JW, KS; formal analysis, CPB, SL; writing—original draft preparation and writing CPB; reviewing and editing, CPB, JSCA, JW, SL, HW. All authors have read and agreed to the published version of the manuscript.
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Baker, C.P., Laba, S., Warner, J. et al. Candida albicans infection suppresses lipopolysaccharide or Pseudomonas aeruginosa stimulated murine bone marrow derived macrophage (BMDM) responses. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39429-z
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DOI: https://doi.org/10.1038/s41598-026-39429-z
