Mapping the mutual transcriptional responses during Candida albicans and human macrophage interactions by dual RNA-sequencing

• Published in: Microbial pathogenesis 2022-12, Vol.173, p.105864-105864, Article 105864
• Main Authors: Rai, Maruti Nandan, Parsania, Chirag, Rai, Rikky
• Format: Article
• Language: English
• Subjects: Candida albicans; Carbon metabolism; Dual RNA sequencing; Human macrophages; Immune response; Signalling pathways and inflammation
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2022.105864

Candida albicans is the leading human fungal pathogen that can cause mucosal and systemic fungal infections. Host phagocytes are the primary immune defense against invading fungal pathogens including C. albicans. To better understand the host-pathogen interaction between C. albicans and host phagocytes, we utilized a human macrophage model of THP-1 macrophages and examined the mutual transcriptomic response of C. albicans and host macrophages by dual RNA-sequencing. Both C. albicans and macrophages displayed marked changes in their transcriptional profiles post 2 h coincubation. We show that C. albicans responds to human macrophages differently than its known response to murine macrophages. C. albicans displays upregulation of its translational machinery and downregulation of glyoxylate and tricarboxylic acid (TCA) cycle upon macrophage phagocytosis. C. albicans triggered strong induction of genes associated with cell surface-mediated signaling and proinflammatory response in THP-1 macrophages. Finally, our data reveal that IL-1β and TNF signaling are central in mounting a proinflammatory response against C. albicans via MAP kinase, and chemokines and cytokines mediated signaling. Overall, current work uncovers the mutual responses of C. albicans and human macrophages towards each other presenting a better understanding of their interaction during C. albicans infections. •Mutual transcriptomic responses of Candida albicans and host macrophages were examined in a human macrophage model.•The transcriptional response of C. albicans to human macrophages is distinctive compared to that for murine macrophages.•C. albicans upregulates its cellular translation and downregulates glyoxylate and TCA cycles upon macrophage phagocytosis.•IL-1β and TNF signaling are central in mounting a proinflammatory response against C. albicans.