Dectin-1 and its role in antifungal immunity

Kimberg, Matti; Brown, Gordon D.

doi:10.1080/13693780802140907

Cited by 44 publications

(36 citation statements)

References 72 publications

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“…Our data are in agreement with other studies demonstrating that Dectin-1 recognizes particulate and soluble ␤-glucan (27) for a number of fungal species (36). Our results demonstrating that ␤ 2 -integrin, TLR2, and Dectin-1 are required for Hc, F1,and ␤-glucan recognition and LB formation suggest that a complex interaction occurs between fungi and cells from the immune system and that this interaction appears to be necessary for signaling to take place.…”

Section: Discussionsupporting

confidence: 83%

Histoplasma capsulatum Cell Wall β-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection

Sorgi

Secatto

Fontanari

et al. 2009

The Journal of Immunology

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Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of worldwide significance. Infection with Hc produces a broad spectrum of diseases and may progress to a life-threatening systemic disease, particularly in individuals with HIV infection. Resolution of histoplasmosis is associated with the activation of cell-mediated immunity, and leukotriene B4 plays an important role in this event. Lipid bodies (LBs) are increasingly being recognized as multifunctional organelles with roles in inflammation and infection. In this study, we investigated LB formation in histoplasmosis and its putative function in innate immunity. LB formation in leukocytes harvested from Hc-infected C57BL/6 mice peaks on day 2 postinfection and correlates with enhanced generation of lipid mediators, including leukotriene B4 and PGE2. Pretreatment of leukocytes with platelet-activating factor and BLT1 receptor antagonists showed that both lipid mediators are involved in cell signaling for LB formation. Alveolar leukocytes cultured with live or dead Hc also presented an increase in LB numbers. The yeast alkali-insoluble fraction 1, which contains mainly β-glucan isolated from the Hc cell wall, induced a dose- and time-dependent increase in LB numbers, indicating that β-glucan plays a signaling role in LB formation. In agreement with this hypothesis, β-glucan-elicited LB formation was inhibited in leukocytes from 5-LO−/−, CD18low and TLR2−/− mice, as well as in leukocytes pretreated with anti-Dectin-1 Ab. Interestingly, human monocytes from HIV-1-infected patients failed to produce LBs after β-glucan stimulation. These results demonstrate that Hc induces LB formation, an event correlated with eicosanoid production, and suggest a role for these lipid-enriched organelles in host defense during fungal infection.

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Section: Discussionsupporting

confidence: 83%

Histoplasma capsulatum Cell Wall β-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection

Sorgi

Secatto

Fontanari

et al. 2009

The Journal of Immunology

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“…These studies identified numerous host PRRs, including Dectin-1, mannose receptor, and CD11b, that were involved in mediating phagocytosis (7). Interactions between the host PRR Dectin-1 and fungal PAMP ␤-(1,3)-glucan were shown to be particularly important for host defense against a variety of pathogenic fungi (7,25,28). We confirmed that ␤-(1,3)-glucan was accessible on the surface of C. neoformans spores (Fig.…”

Section: Resultssupporting

confidence: 66%

Elucidating the Pathogenesis of Spores from the Human Fungal PathogenCryptococcus neoformans

et al. 2009

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Cryptococcus neoformans was first described as a human fungal pathogen more than a century ago. One aspect of the C. neoformans infectious life cycle that has been the subject of earnest debate is whether the spores are pathogenic. Despite much speculation, no direct evidence has been presented to resolve this outstanding question. We present evidence that C. neoformans spores are pathogenic in a mouse intranasal inhalation model of infection. In addition, we provide mechanistic insights into spore-host interactions. We found that C. neoformans spores were phagocytosed by alveolar macrophages via interactions between fungal ␤-(1,3)-glucan and the host receptors Dectin-1 and CD11b. Moreover, we discovered an important link between spore survival and macrophage activation state: intracellular spores were susceptible to reactive oxygen-nitrogen species. We anticipate these results will serve as the basis for a model to further investigate the pathogenic implications of infections caused by fungal spores.

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“…The studies reported herein demonstrate that the major markers of macrophage activation can be categorized as early (maximum at 6 h) or late (evident at 24 h) and their Similarly, the mannose and dectin-1 receptors are involved in the recognition of mannose residues on pathogens [20] and b-glucans on fungal pathogens [32][33][34], respectively, and are early markers of alternative activation. In contrast, the ym1 and fizz1 gene products, chitnase [48] and resistinlike proteins [49], respectively, that are involved in wound healing and tissue repair are late markers of alternative activation.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, alternative activation has been associated with arginase 1, fizz1 and ym1 that are involved in tissue repair, control of some parasitic infections and control of reactive nitrogen intermediates [6,7,10,27,29,30]. However, these macrophages are also associated with the expression of the mannose receptor [3] and dectin-1 [4], which are important in pathogen recognition and have been demonstrated to play a beneficial role in fungal infections [31][32][33][34][35]. More recently it has been suggested that activated macrophages comprise a spectrum based on three major activities; classically activated (as described previously), wound-healing (stimulated with IL-4 or IL-13) and regulatory, which are induced by TLR ligation in combination with other stimuli, including immune complexes [21].…”

Section: Discussionmentioning

confidence: 99%

Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation

Menzies

Henriquez

Alexander

et al. 2010

Clinical and Experimental Immunology

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SummaryThe present study examines the temporal dynamics of macrophage activation marker expression in response to variations in stimulation. We demonstrate that markers can be categorized as 'early' (expressed most abundantly at 6 h post-stimulation) or 'late' (expressed at 24 h post-stimulation). Thus nos2 and p40 (IL-12/IL-23) are early markers of innate and classical activation, while dectin-1 and mrc-1 are early markers and fizz1 (found in inflammatory zone-1) and ym1 are late markers of alternative activation. Furthermore, argI is a late marker of both innate and alternative activation. The ability of interferon (IFN)-g to alter these activation markers was studied at both the protein level and gene level. As reported previously, IFN-g was able to drive macrophages towards the classical phenotype by enhancing nos2 gene expression and enzyme activity and p40 (IL-12/IL-23) gene expression in lipopolysaccharide (LPS)-stimulated macrophages. IFN-g antagonized alternative macrophage activation, as evident by reduced expression of dectin-1, mrc-1, fizz1 and ym1 mRNA transcripts. In addition, IFN-g antagonized arginase activity irrespective of whether macrophages were activated innately or alternatively. Our data explain some apparent contradictions in the literature, demonstrate temporal plasticity in macrophage activation states and define for the first time 'early' and 'late' markers associated with anti-microbial/inflammatory and wound healing responses, respectively.

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Dectin-1 and its role in antifungal immunity

Cited by 44 publications

References 72 publications

Histoplasma capsulatum Cell Wall β-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection

Histoplasma capsulatum Cell Wall β-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection

Elucidating the Pathogenesis of Spores from the Human Fungal PathogenCryptococcus neoformans

Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation

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