Stage-Specific Sampling by Pattern Recognition Receptors during Candida albicans Phagocytosis

Heinsbroek, Sigrid E. M.; Taylor, Philip Russel; Martínez, Fernando O.; Martı́nez-Pomares, Luisa; Brown, Gordon D.; Gordon, Siamon

doi:10.1371/journal.ppat.1000218

Cited by 114 publications

(102 citation statements)

References 76 publications

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“…b-Glucan drives BM-DC maturation at least in part through dectin-1, which is considered a major PRR for glucans (37). However, in this study we show that the C. glabrata-induced IFN-b release is independent of dectin-1 and CD11b, both acting as b-glucan receptors accumulating at the site of Candida uptake by macrophage phagocytosis (52). Furthermore, we tend to exclude the involvement of other unknown b-glucan receptors, because all of the b-glucan preparations that we used, namely, b-1,3-and b-1,6-glucan extracts obtained from the S. cerevisiae cell wall, and Curdlan, a linear b-1,3-glucan polymer, fail to trigger an IFN-b release in BM-DCs.…”

Section: Discussioncontrasting

confidence: 55%

Conventional Dendritic Cells Mount a Type I IFN Response againstCandidaspp. Requiring Novel Phagosomal TLR7-Mediated IFN-β Signaling

Bourgeois

Majer

Frohner

et al. 2011

The Journal of Immunology

109

101

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Human fungal pathogens such as the dimorphic Candida albicans or the yeast-like Candida glabrata can cause systemic candidiasis of high mortality in immunocompromised individuals. Innate immune cells such as dendritic cells and macrophages establish the first line of defense against microbial pathogens and largely determine the outcome of infections. Among other cytokines, they produce type I IFNs (IFNs-I), which are important modulators of the host immune response. Whereas an IFN-I response is a hallmark immune response to bacteria and viruses, a function in fungal pathogenesis has remained unknown. In this study, we demonstrate a novel mechanism mediating a strong IFN-β response in mouse conventional dendritic cells challenged by Candida spp., subsequently orchestrating IFN-α/β receptor 1-dependent intracellular STAT1 activation and IFN regulatory factor (IRF) 7 expression. Interestingly, the initial IFN-β release bypasses the TLR 4 and TLR2, the TLR adaptor Toll/IL-1R domain-containing adapter-inducing IFN-β and the β-glucan/phagocytic receptors dectin-1 and CD11b. Notably, Candida-induced IFN-β release is strongly impaired by Src and Syk family kinase inhibitors and strictly requires completion of phagocytosis as well as phagosomal maturation. Strikingly, TLR7, MyD88, and IRF1 are essential for IFN-β signaling. Furthermore, in a mouse model of disseminated candidiasis we show that IFN-I signaling promotes persistence of C. glabrata in the host. Our data uncover for the first time a pivotal role for endosomal TLR7 signaling in fungal pathogen recognition and highlight the importance of IFNs-I in modulating the host immune response to C. glabrata.

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Section: Discussioncontrasting

confidence: 55%

Conventional Dendritic Cells Mount a Type I IFN Response againstCandidaspp. Requiring Novel Phagosomal TLR7-Mediated IFN-β Signaling

Bourgeois

Majer

Frohner

et al. 2011

The Journal of Immunology

109

101

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“…5,6 This receptor recognizes b-1,3-glucans that are exposed on particles such as zymosan and many fungi, including species of Candida, Aspergillus and Pneumocystis, [7][8][9] either alone or in conjunction with other PRRs, most notably TLR2 and the mannose receptor. 10 As the principal non-opsonic receptor involved in fungal uptake, 11 dectin-1 engagement mediates cell activation, cytokine production and a variety of antifungal responses through the spleen tyrosine kinase (Syk)/caspase recruitment domain-containing protein 9-dependent pathway. 12 Recently, dectin-1 was also shown to signal through Raf-1 and both Syk-and Raf-1-dependent pathways, converging at the level of NF-kB activation to control adaptive immunity to fungi.…”

Section: Introductionmentioning

confidence: 99%

Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

et al. 2012

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The recognition of b-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/ noncanonical NF-kB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling.

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“…The macrophage MR, one of the best characterized C-type lectin receptor (CLR) was the first membrane receptor implicated in the recognition of Candida yeasts by human macrophages [43,44,[51][52][53]. Monocyte-derived human macrophages (MDM) ingested and killed unopsonized Candida blastoconidia but both phagocytosis and killing of unopsonized yeasts were slower than those of serum-opsonized Candida [42].…”

Section: Induction Of Th17 Differentiation By Pattern Recognition Recmentioning

confidence: 99%

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans

Soltész

Töth

Sarkadi

et al. 2015

International Reviews of Immunology

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Stage-Specific Sampling by Pattern Recognition Receptors during Candida albicans Phagocytosis

Cited by 114 publications

References 76 publications

Conventional Dendritic Cells Mount a Type I IFN Response againstCandidaspp. Requiring Novel Phagosomal TLR7-Mediated IFN-β Signaling

Conventional Dendritic Cells Mount a Type I IFN Response againstCandidaspp. Requiring Novel Phagosomal TLR7-Mediated IFN-β Signaling

Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans

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