Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects

Gazendam, Roel P.; Hamme, John L. van; Tool, Anton T.J.; Houdt, Michel van; Verkuijlen, Paul; Herbst, Martin; Liese, Johannes G.; Veerdonk, Frank L. van de; Roos, Dirk; Berg, Timo K. van den; Kuijpers, Taco W.

doi:10.1182/blood-2014-01-551473

Cited by 155 publications

(168 citation statements)

References 42 publications

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“…32 CLRs induce signaling and ROS formation via the NADPH oxidase system, which result in neutrophilmediated killing of C. albicans. 33 Our results showed that neutrophils also killed C. glabrata through an augmented respiratory burst (Fig. 2).…”

Section: Discussionmentioning

confidence: 71%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 71%

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

et al. 2017

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“…Neutrophils contribute to the initial steps of fungal killing, which plays a special role in neutropenic and immunosuppressed populations (36,45). CARD9 signaling and ROS formation by the NADPH oxidase system were involved in neutrophil killing of C. albicans (46). CR3 and the Dectin-1 receptor have been reported to be able to recognize cell wall ␤-glucan of C. albicans and mediate killing (46).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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bFungi can shield surface pathogen-associated molecular patterns (PAMPs) for evading host immune attack. The most common and opportunistic human pathogen, Candida albicans, can shield ␤-(1 3)-glucan on the cell wall, one of the major PAMPs, to avoid host phagocyte Dectin-1 recognition. The way to interfere in the shielding process for more effective antifungal defense is not well established. In this study, we found that deletion of the C. albicans GPI7 gene, which was responsible for adding ethanolaminephosphate to the second mannose in glycosylphosphatidylinositol (GPI) biosynthesis, could block the attachment of most GPI-anchored cell wall proteins (GPI-CWPs) to the cell wall and subsequently unmask the concealed ␤-(1,3)-glucan. Neutrophils could kill the uncloaked gpi7 mutant more efficiently with an augmented respiratory burst. The gpi7 mutant also stimulated Dectin-1-dependent immune responses of macrophages, including activation of nuclear factor-B (NF-B) and mitogenactivated protein kinase (MAPK) pathways and secretion of specific cytokines, such as tumor necrosis factor alpha (TNF-␣), interleukin 6 (IL-6), and IL-12p40. Furthermore, the gpi7 null mutant could induce an enhanced inflammatory response through promoting significant recruitment of neutrophils and monocytes and could stimulate stronger Th1 and Th17 cell responses to fungal infections in vivo. These in vivo phenotypes also were Dectin-1 dependent. Thus, we assume that GPI-CWPs are involved in the immune mechanism of C. albicans escaping from host recognition by Dectin-1. Our studies also indicate that the blockage of GPI anchor synthesis is a strategy to inhibit C. albicans evading host recognition.

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“…Fungi are recognized via PRRs, particularly C-type-lectin receptors (CLRs), Toll-like receptors (TLRs), and complement receptor 3 (CR3) (7)(8)(9). TLR signaling appears redundant for human antifungal host defense, as patients with myeloid differentiation primary response 88 (MYD88) and interleukin-1 receptor-associated kinase 4 (IRAK4) mutations develop pyogenic bacterial but not fungal infections (10).…”

Section: Introductionmentioning

confidence: 99%

Extrapulmonary Aspergillus infection in patients with CARD9 deficiency

et al. 2016

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Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects

Abstract: Key Points Human neutrophils use 2 independent mechanisms for the killing of unopsonized and serum-opsonized C albicans. Unopsonized Candida killing depends on CR3 and CARD9 but not dectin-1; opsonized Candida killing on FcγR, PKC, and NADPH oxidase activity.

Cited by 155 publications

References 42 publications

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

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

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

Extrapulmonary Aspergillus infection in patients with CARD9 deficiency

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