The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

Reedy, Jennifer L.; Negoro, Paige; Feliu, Marianela; Lord, Allison; Khan, Nida S.; Lukason, Daniel P; Wiederhold, Nathan P.; Tam, Jenny M.; Mansour, Michael K.; Patterson, Thomas F.; Vyas, Jatin M.

doi:10.1128/iai.00903-16

Cited by 11 publications

(18 citation statements)

References 77 publications

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“…MTT assay indicated that THP-1 cells did not damage significantly the Curvularia strains. Similarly, macrophages could not inhibit conidial germination and hyphal growth of E. rostratum ( 29 ). At the same time, THP-1 cells effectively decreased the viability of A. fumigatus during their interaction, as expected based on previous studies ( 20 ).…”

Section: Discussionmentioning

confidence: 98%

“…Although there are no available data about the response of monocytes to any similar dematiaceous mold, there are a few studies discussing the interaction of these fungi with other cell types. Recently, Reedy et al ( 29 ) found that macrophages could not phagocytose the conidia of Exserohilum rostratum , another dematiaceous mold related to Curvularia . At the same time, macrophages also showed an attraction and attachment to the hyphae of Exserohilum .…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, macrophages also showed an attraction and attachment to the hyphae of Exserohilum . The different affinity of macrophages to the conidia and the hyphae was explained by the possibly different polysaccharide composition of the cell walls ( 29 ). Besides phagocytosis, only touching and dragging of the fungal cells, conidia and hyphal elements by macrophages to prevent the spread of the fungus into the different tissues was proven in cases of A. fumigatus and C. albicans ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

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Interaction of THP-1 Monocytes with Conidia and Hyphae of Different Curvularia Strains

et al. 2017

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Interaction of the human monocytic cell line, THP-1 with clinical isolates of three Curvularia species were examined. Members of this filamentous fungal genus can cause deep mycoses emerging in both immunocompromised and immunocompetent patients. It was found that monocytes reacted only to the hyphal form of Curvularia lunata. Cells attached to the germ tubes and hyphae and production of elevated levels of interleukin (IL)-8 and IL-10 and a low level of TNF-α were measured. At the same time, monocytes failed to produce IL-6. This monocytic response, especially with the induction of the anti-inflammatory IL-10, correlates well to the observation that C. lunata frequently cause chronic infections even in immunocompetent persons. Despite the attachment to the hyphae, monocytes could not reduce the viability of the fungus and the significant decrease in the relative transcript level of HLA-DRA assumes the lack of antigen presentation of the fungus by this cell type. C. spicifera and C. hawaiiensis failed to induce the gathering of the cells or the production of any analyzed cytokines. Monocytes did not recognize conidia of Curvularia species, even when melanin was lacking in their cell wall.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interaction of THP-1 Monocytes with Conidia and Hyphae of Different Curvularia Strains

et al. 2017

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“…A polarizer (Nikon, MEN 51941) and Wollaston prisms (Nikon, MBH76190) were used to acquire differential interference contrast (DIC) images. Emission light from the samples was collected after passage through the appropriate emission filters (Semrock, Rochester, NY, USA) ( 32 ). Images were acquired using MetaMorph software (Molecular Devices, Downingtown, PA, USA), and processed using Adobe Photoshop CS5 and assembled in Adobe Illustrator, version CS5 (Adobe Systems, San Jose, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Fluorescent Tracking of Yeast Division Clarifies the Essential Role of Spleen Tyrosine Kinase in the Intracellular Control of Candida glabrata in Macrophages

Dagher

Negoro

et al. 2018

Front. Immunol.

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Macrophages play a critical role in the elimination of fungal pathogens. They are sensed via cell surface pattern-recognition receptors and are phagocytosed into newly formed organelles called phagosomes. Phagosomes mature through the recruitment of proteins and lysosomes, resulting in addition of proteolytic enzymes and acidification of the microenvironment. Our earlier studies demonstrated an essential role of Dectin-1-dependent activation of spleen tyrosine kinase (Syk) in the maturation of fungal containing phagosomes. The absence of Syk activity interrupted phago-lysosomal fusion resulting in arrest at an early phagosome stage. In this study, we sought to define the contribution of Syk to the control of phagocytosed live Candida glabrata in primary macrophages. To accurately measure intracellular yeast division, we designed a carboxyfluorescein succinimidyl ester (CFSE) yeast division assay in which bright fluorescent parent cells give rise to dim daughter cells. The CFSE-labeling of C. glabrata did not affect the growth rate of the yeast. Following incubation with macrophages, internalized CFSE-labeled C. glabrata were retrieved by cellular lysis, tagged using ConA-647, and the amount of residual CFSE fluorescence was assessed by flow cytometry. C. glabrata remained undivided (CFSE bright) for up to 18 h in co-culture with primary macrophages. Treatment of macrophages with R406, a specific Syk inhibitor, resulted in loss of intracellular control of C. glabrata with initiation of division within 4 h. Delayed Syk inhibition after 8 h was less effective indicating that Syk is critically required at early stages of macrophage–fungal interaction. In conclusion, we demonstrate a new method of tracking division of C. glabrata using CFSE labeling. Our results suggest that early Syk activation is essential for macrophage control of phagocytosed C. glabrata.

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“…Not much work has been done to elucidate the mechanism of infection and immune responses against these fungi. A very recent work demonstrates the role of Dectin-1 in the recognition of Exserohilum rostratum ( 30 ). Mouse macrophages generate a Dectin-1 dependent TNF-α, IL-1β, MIP-1, and MIP-2 secretion in response to E. rostratum hyphae in vitro and the response is diminished in Dectin-1-deficient macrophages.…”

Section: Rare Disease Causing Fungimentioning

confidence: 98%

The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors

et al. 2018

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Fungi, usually present as commensals, are a major cause of opportunistic infections in immunocompromised patients. Such infections, if not diagnosed or treated properly, can prove fatal. However, in most cases healthy individuals are able to avert the fungal attacks by mounting proper antifungal immune responses. Among the pattern recognition receptors (PRRs), C-type lectin receptors (CLRs) are the major players in antifungal immunity. CLRs can recognize carbohydrate ligands, such as β-glucans and mannans, which are mainly found on fungal cell surfaces. They induce proinflammatory immune reactions, including phagocytosis, oxidative burst, cytokine, and chemokine production from innate effector cells, as well as activation of adaptive immunity via Th17 responses. CLRs such as Dectin-1, Dectin-2, Mincle, mannose receptor (MR), and DC-SIGN can recognize many disease-causing fungi and also collaborate with each other as well as other PRRs in mounting a fungi-specific immune response. Mutations in these receptors affect the host response and have been linked to a higher risk in contracting fungal infections. This review focuses on how CLRs on various immune cells orchestrate the antifungal response and on the contribution of single nucleotide polymorphisms in these receptors toward the risk of developing such infections.

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The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

Cited by 11 publications

References 77 publications

Interaction of THP-1 Monocytes with Conidia and Hyphae of Different Curvularia Strains

Interaction of THP-1 Monocytes with Conidia and Hyphae of Different Curvularia Strains

Fluorescent Tracking of Yeast Division Clarifies the Essential Role of Spleen Tyrosine Kinase in the Intracellular Control of Candida glabrata in Macrophages

The Interaction of Human Pathogenic Fungi With C-Type Lectin Receptors

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