Abstract
Candida albicans, a commonly encountered fungal pathogen, causes diseases varying from superficial mucosal complaints to life-threatening systemic disorders. Among the virulence traits of C. albicans, yeast-to-hypha transition is most widely acknowledged. Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs), and defence against C. albicans infection is provided by an exquisite interplay between the innate and adaptive arms of the host immune system.
Keywords: antifungal, Candida albicans, immune response
Fungal infections in the human population have risen substantially in the past several decades.1 This increase is largely due to the AIDS pandemic and some advents in modern medicine, including massive chemotherapy, organs transplantation, immunosuppression, and implantable medical devices. Candida albicans is a commonly encountered fungal pathogen. It may cause diseases varying from superficial mucosal infections to systemic disorders with high mortality rate. Notably, clinical available antifungal agents are limited, and drug resistance is a significant challenge.2
Yeast-to-hypha transition is a widely acknowledged virulence trait of C. albicans. The transition is controlled by multiple regulatory circuits, among which the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway plays a major role. A central component of the cAMP/PKA pathway is Cyr1 (also known as Cdc35), the sole adenylyl cyclase of C. albicans that catalyzes cAMP synthesis. To investigate how Cyr1 activity is regulated, the identification of interacting partners of Cyr1 will definitely provide some important information.3
C. albicans is a commensal fungus that colonizes on genital/gastrointestinal mucosa without causing disease, and only in immunosuppressed hosts can C. albicans become pathogenic. The interaction between C. albicans and the host immune system plays an important role in both commensalism and infection. In recent years, more and more studies have focused on immune defense mechanisms against C. albicans.
Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs).4 PRRs are involved in the recognition of C. albicans in epithelial cells, neutrophils, endothelial cells, monocytes/macrophages, dendritic cells (DCs), etc. The present known PRRs of C. albicans include Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), among which CLRs and TLRs are major. Of note, Dectin-1, one of the CLRs, recognizes β-glucans on cell wall of C. albicans, and the rest CLRs recognize different mannose-relative structures. Ligation of Dectin-1 can stimulate a variety of cellular responses, including activation of nuclear transcription factor NF-κB and IRF5, ERK-MAPK pathway, NLRP3 inflammasome, phagocytosis, respiratory burst and Rubicon. Interestingly, Dectin-1 can collaborate with TLRs to orchestrate antifungal immunity.5
During C. albicans bloodstream infection, which may present as sepsis and septic shock, innate responses govern the early response. Neutrophils are considered principal effector cells conferring protection. Neutrophil activation is closely linked to complement and modulated by activated mononuclear cells. A thorough understanding of these mechanisms is helpful to treat patients suffering from systemic candidiasis.6
Defense against C. albicans infection is provided by an exquisite interplay between the innate and adaptive arms of the host immune system. DCs are specialized antigen presenting cells (APCs) and serve as a critical conduit between the innate and adaptive immune responses. T-cells are an integral component of the host adaptive immune response to C. albicans, and the Th1 and Th17 cellular responses play a central role.1
Based on the findings on antifungal immune response, some progress has been obtained on developing C. albicans vaccines, including live attenuated C. albicans strain, protein vaccines, and glycoconjugates vaccines. Although the currently available vaccines have been demonstrated protective, some more efforts are still needed to achieve a vaccine applicable in patients.7
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Funding
YW is sponsored by the National Natural Science Foundation of China (81273558) and the Shanghai Pujiang Program (14PJD001).
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