Dectin-1 plays an important role in host defense against systemicCandida glabratainfection

Abstract

Candida glabrata is the second most common pathogen of severe candidiasis in immunocompromised hosts, following C. albicans. Although C. glabrata and C. albicans belong to the same genus, they are phylogenetically distinct. C-type lectin receptors (CLRs), acting as patternrecognition receptors (PRRs), play critical roles in host defense against C. albicans infections. However, our understanding of the specific roles of CLRs in host defense against C. glabrata is limited. Here, we explored the potential roles of the C-type lectins Dectin-1 and Dectin-2 in host defense against C. glabrata. We found that both Dectin-1-deficient mice (Dectin-1 ¡/¡ ) and Dectin-2-deficient mice (Dectin-2 ¡/¡ ) are more susceptible to C. glabrata infection. Dectin-1confers host higher sensitivity for sensing C. glabrata infections, while the effect of Dectin-2 in the host defense against C. glabrata is infection dose dependent. Dectin-1 is required for host myeloid cells recognition, killing of C. glabrata, and development of subsequent Th1 and Th17 cell-mediated adaptive immune response. Significantly impaired inflammatory responses such as inflammatory cells recruitment and cytokines release that were induced by C. glabrata were manifested in Dectin-1-deficient mice. Together, our study demonstrates that Dectin-1 plays an important role in host defense against systemic Candida glabrata infections, indicating a previous unknown control mechanism for this particular type of infection in host. Our study, therefore, provides new insights into the host defense against C. glabrata.

Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response

“…β-Glucans have been reported to induce the transcription and secretion of IL-1β via Dectin-1/Syk signaling–dependent activation of the NRLP3 inflammasome in human macrophages ( 41 , 46 ). Importantly, both Dectin-1 and Dectin-2 have recently been implicated in host resistance against systemic C. glabrata infections, as Dectin-1– and 2–deficient mice exhibited elevated susceptibility to C. glabrata infections ( 47 , 48 ). The key finding of involvement of Syk-dependent IL-1β production in intracellular survival in our study is likely to be dependent on extracellular/intracellular sensing of C. glabrata components.…”

The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors

“…The differences in the results may be attributed to different mouse and C. albicans strains used in experiments ( 177 ). Dectin-1-deficient mice also are more susceptible to C. glabrata infections and show impaired inflammatory responses ( 178 ).…”

Scavenger Receptors: Promiscuous Players during Microbial Pathogenesis

“…Dectin-1 (SR-E2) binds to β-glucans from various fungal pathogens, usually protecting the host from infection. Therefore, Dectin-1 KO mice were shown to be more susceptible to infections with Candida albicans, Candida glabrata and Aspergillus fumigatus (Chen et al 2017;Taylor et al 2007;Werner et al 2009). Phagocytosis stimulation, ROS and cytokine production, inflammasome activation and T helper cell differentiation are some of the anti-fungal responses generated by this receptor (Geijtenbeek and Gringhuis 2009).…”