IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival


Autoři: Selim Nur aff001;  Florian Sparber aff001;  Christina Lemberg aff001;  Eva Guiducci aff001;  Tiziano A. Schweizer aff001;  Pascale Zwicky aff002;  Burkhard Becher aff002;  Salomé LeibundGut-Landmann aff001
Působiště autorů: Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland aff001;  Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland aff002
Vyšlo v časopise: IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008115
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008115

Souhrn

The opportunistic fungal pathogen Candida albicans can cause invasive infections in susceptible hosts and the innate immune system, in particular myeloid cell-mediated immunity, is critical for rapid immune protection and host survival during systemic candidiasis. Using a mouse model of the human disease, we identified a novel role of IL-23 in antifungal defense. IL-23-deficient mice are highly susceptible to systemic infection with C. albicans. We found that this results from a drastic reduction in all subsets of myeloid cells in the infected kidney, which in turn leads to rapid fungal overgrowth and renal tissue injury. The loss in myeloid cells is not due to a defect in emergency myelopoiesis or the recruitment of newly generated cells to the site of infection but, rather, is a consequence of impaired survival of myeloid cells at the site of infection. In fact, the absence of a functional IL-23 pathway causes massive myeloid cell apoptosis upon C. albicans infection. Importantly, IL-23 protects myeloid cells from apoptosis independently of the IL-23-IL-17 immune axis and independently of lymphocytes and innate lymphoid cells. Instead, our results suggest that IL-23 acts in a partially autocrine but not cell-intrinsic manner within the myeloid compartment to promote host protection from systemic candidiasis. Collectively, our data highlight an unprecedented and non-canonical role of IL-23 in securing survival of myeloid cells, which is key for maintaining sufficient numbers of cells at the site of infection to ensure efficient host protection.

Klíčová slova:

Bone marrow cells – Candida albicans – Candidiasis – Flow cytometry – Fungal diseases – Kidneys – Monocytes – Neutrophils


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