Dectin-1 Is Not Required for Controlling Candida albicans Colonization of the Gastrointestinal Tract

Abstract

bCandida albicans is normally found as a commensal microbe, commonly colonizing the gastrointestinal tract in humans. However, this fungus can also cause mucosal and systemic infections once immune function is compromised. Dectin-1 is an innate pattern recognition receptor essential for the control of fungal infections in both mice and humans; however, its role in the control of C. albicans colonization of the gastrointestinal tract has not been defined. Here, we demonstrate that in mice dectin-1 is essential for the control of gastrointestinal invasion during systemic infection, with dectin-1 deficiency associating with impaired fungal clearance and dysregulated cytokine production. Surprisingly, however, following oral infection, dectin-1 was not required for the control of mucosal colonization of the gastrointestinal tract, in terms of either fungal burdens or cytokine response. Thus, in mice, dectin-1 is essential for controlling systemic infection with C. albicans but appears to be redundant for the control of gastrointestinal colonization.

Murine Models of Candida Gastrointestinal Colonization and Dissemination

“…Two studies have implicated the importance of dectin-1 in controlling C. albicans GI colonization (81,84). Yet, in another recent study, there was no significant difference in Candida GI colonization between wild-type and dectin-1-deficient mice (85), but this was observed only when the wild-type and dectin-1-deficient mice were housed together in the same cage. The disparate results reported from these studies may be due to variations in the microbiota of the mice: there was no cohousing in the first two experiments and different sources for these animals.…”

Fungal β-Glucan, a Dectin-1 Ligand, Promotes Protection from Type 1 Diabetes by Inducing Regulatory Innate Immune Response

“…However, recent reports have shown that the β-glucan receptor, Dectin-1 has a redundant role in protective responses against certain fungal infections, and β-glucan rich ligand induced immunomodulatory response against systemic Staphylococcus infection as well as in zymosan induced multiple organ dysfunction syndrome (9-11). Our observations that β-glucan induced innate immunity can promote Treg and Th17 and Th2 responses demonstrate the immune regulatory nature of Dectin-1 dependent innate immune response and confirm the redundant role of Dectin-1, especially in conditions that involve strong inflammatory and Th1 responses.…”

“…Studies have shown that β-glucan can activate both the innate and adaptive immunity and hence, can be used as an effective adjuvant in immunotherapies for treatment of cancer and infections (3, 4). However, recent studies have shown that the role of Dectin-1 in immune potentiation activities of β-glucan rich ligands against some bacterial and fungal infections is redundant (9-11). …”

Abolishing Cell Wall Glycosylphosphatidylinositol-Anchored Proteins in Candida albicans Enhances Recognition by Host Dectin-1

“…C57BL/6 mice were obtained from Shanghai Laboratory Animal Center of the Chinese Academy of Sciences. Dectin-1-deficient mice on a C57BL/6 background were kindly provided by Gordon D. Brown (the Dectin-1-deficient mice were generated on a mixed 129/Sv ϫ C57BL/6 genetic background in Gordon Brown's laboratory and backcrossed for nine generations on the C57BL/6 background) (25). All of the animal experiments were performed in compliance with institutional guidelines and according to the protocol approved by the Institutional Animal Use and Care Committee of Tongji University.…”