Immunity against fungi

Lionakis, Michail S.; Iliev, Iliyan D.; Hohl, Tobias M.

doi:10.1172/jci.insight.93156

Cited by 105 publications

(78 citation statements)

References 200 publications

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“…Dectin-1 and -2 are CLRs that respectively bind the fungal cell wall polysaccharides bglucans and mannans and both activate the kinase Syk either directly (Dectin-1) or through the FcRg chain (Dectin-2) (19)(20)(21). We employed preparations of b-glucans and mannans isolated from Candida albicans that exhibit distinct physical forms being respectively insoluble with a diameter of ~500 nm and soluble with a diameter of ~20 nm (Fig.…”

Section: Resultsmentioning

confidence: 99%

The physical form of microbial ligands bypasses the need for dendritic cell migration to stimulate adaptive immunity

Borriello

Spreafico

Poli

et al. 2020

Preprint

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A central paradigm of immunology is that the innate immune system first detects infectious agents in peripheral tissues, shortly after a pathogen has breached an epithelial barrier. This detection event is mediated by pattern recognition receptors in phagocytes, which then migrate to draining lymph nodes (dLNs), where information of a microbial encounter is conveyed to T and B lymphocytes to generate adaptive immunity. Through the study of fungal moieties, we present data that challenge this model. We found that soluble fungal polysaccharides are immunosilent in the periphery, but become potent immunogens in the dLN. These ligands completely bypass the need of phagocyte migration and, instead, directly activate an immune response that is most similar to those that typify viral infections. These data establish a class of microbial products that violate a central tenet of the immunological lexicon and illustrate that the physical form (not just the chemical structure) impacts innate and adaptive immunity. Short title (40 characters):The form of PAMPs dictates immunity

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Section: Resultsmentioning

confidence: 99%

The physical form of microbial ligands bypasses the need for dendritic cell migration to stimulate adaptive immunity

Borriello

Spreafico

Poli

et al. 2020

Preprint

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“…Mannans and mannosylated moieties are recognized by a variety of CLRs including dectin-2, mincle, mannose receptor (MR), and DC-SIGN [5,11]. Of these, MR does not seem to signal upon binding to its ligand (N-linked Candida mannans) nor does it seem to be required in the experimental models of fungal infection [5,11], although it might play a role in the polarization of human Th17 cells [39]. DC-SIGN recognizes a variety of carbohydrate including N-linked mannosyl residues of Candida [40].…”

Section: Dectin-2 Dectin-3 Fcrγ Fcrγmentioning

confidence: 99%

“…DC‐SIGN activates RAF‐1 which in turn modulates NF‐κB transcriptional program [41]. The outcome of DC‐SIGN signaling seems to vary according to the triggering stimulus and concurrent activation of other PRRs as well [5,11]. At variance with MR and DC‐SIGN, mincle and dectin‐2 signal through the SYK/CARD9 pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Instead, mincle activation leads to SYK/CARD9‐dependent activation of the PI3K/AKT pathway that is required for activation of the E3 ubiquitin ligase MDM2 and proteasomal degradation of IRF1 [43]. Dectin‐2 recognizes α‐mannans and α‐1,2‐mannosylated residues of several fungal species [5,11]. Although the responses elicited by dectin‐1 and dectin‐2 may exhibit some degree of overlap, signaling pathways activated by dectin‐2 have been less intensively investigated compared to dectin‐1 and require further studies.…”

Section: Introductionmentioning

confidence: 99%

“…fungal size) [4]. Fungal ligands activate a variety of pattern recognition receptors (PRRs) including C-type lectin receptors (CLRs), Toll-like receptors (TLRs), and NOD-like receptors [5]. Interestingly, primary immunodeficiencies of TLR and NOD-like receptor pathways do not increase the risk of fungal infections, while deficiencies of the CLR CLEC7A (dectin-1) or the signaling molecule CARD9 downstream to many CLRs are linked to chronic mucocutaneous candidiasis (although a causative connection for CLEC7A has not been fully established) and, in the case of CARD9 deficiency, also to systemic fungal diseases [6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cellular and molecular mechanisms of antifungal innate immunity at epithelial barriers: The role of C‐type lectin receptors

2020

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Humans are constantly exposed to fungi, either in the form of commensals at epithelial barriers or as inhaled spores. Innate immune cells play a pivotal role in maintaining commensal relationships and preventing skin, mucosal, or systemic fungal infections due to the expression of pattern recognition receptors that recognize fungal cell wall components and modulate both their activation status and the ensuing adaptive immune response. Commensal fungi also play a critical role in the modulation of homeostasis and disease susceptibility at epithelial barriers. This review will outline cellular and molecular mechanisms of anti‐fungal innate immunity focusing on C‐type lectin receptors and their relevance in the context of host‐fungi interactions at skin and mucosal surfaces in murine experimental models as well as patients susceptible to fungal infections.

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Immunity to Fungi

Michalski

Sadarangani

Lavoie

2018

Encyclopedia of Life Sciences

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Fungi are microorganisms that are ubiquitous in the environment. To establish themselves in the host, they employ a broad variety of virulence strategies. Fungi are an important source of morbidity in humans. However, despite millions of species, only about a hundred cause disease, owing to a remarkable collaboration of the innate and adaptive immune systems. In individuals who have immunocompromised cellular immunity, fungi readily cause invasive disease. Our knowledge of how the immune system prevents invasive fungal disease has been greatly aided by the study of acquired or inherited immune defects. However, much remains to be known in order to improve our ability to treat fungal infections, and our ability to control endemic disease in many areas of the world remains limited, warranting more research towards immunomodulatory interventions. Key Concepts Fungi readily colonise the environment including our skin and mucosal surfaces. Invasive fungal infections largely occur in individuals with impaired immunity, although infections are endemic in many areas of the world in immunocompetent hosts. T cells and neutrophils are essential in preventing invasive fungal disease. In immunocompromised hosts, fungi frequently cause disease by direct invasion, and also indirectly (i.e. through exaggerated host immune responses). Fungal infections are a major cause of morbidity and mortality worldwide.

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Immunity against fungi

Cited by 105 publications

References 200 publications

The physical form of microbial ligands bypasses the need for dendritic cell migration to stimulate adaptive immunity

The physical form of microbial ligands bypasses the need for dendritic cell migration to stimulate adaptive immunity

Cellular and molecular mechanisms of antifungal innate immunity at epithelial barriers: The role of C‐type lectin receptors

Immunity to Fungi

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