Involvement of CD14 and Toll-Like Receptors in Activation of Human Monocytes by<i>Aspergillus fumigatus</i>Hyphae

Wang, J. E.; Warris, Adilia; Ellingsen, Espen B.; Jørgensen, Per; Flo, Trude Helen; Espevik, Terje; Solberg, Rigmor; Verweij, Paul E.; Aasen, Ansgar O.

doi:10.1128/iai.69.4.2402-2406.2001

Cited by 211 publications

(156 citation statements)

References 39 publications

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“…Although in vitro studies have indicated the importance of TLR signaling in response to Candida and Aspergillus (21)(22)(23)(24)(25)(26)(27)(28), the role of TLRs in the generation of innate and adaptive immunity to fungi remains largely undefined. We show in this study that 1) the MyD88-dependent pathway is essentially required for the innate and Th1-mediated resistance to either fungus; 2) the involvement of MyD88 may occur through signaling by distinct TLRs depending upon the fungal species, morphotypes, and site of infection; and 3) TLRs may contribute differently to the occurrence of innate and adaptive Th1 immunities to each fungus, consistent with the ability of each individual TLR to activate specialized antifungal effector functions on PMNs and DCs.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of fungi, in vitro studies have shown that Cryptococcus neoformans, C. albicans, and A. fumigatus may signal through TLRs, particularly TLR2, TLR4, and TLR9, in a morphotype-specific fashion (21)(22)(23)(24)(25)(26)(27)(28)). This will not come as a surprise, given the initial discovery of the Toll pathway in Drosophila as an essential mechanism of antifungal resistance (29).…”

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confidence: 99%

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The Contribution of the Toll-Like/IL-1 Receptor Superfamily to Innate and Adaptive Immunity to Fungal Pathogens In Vivo

Bellocchio

Montagnoli

Bozza

et al. 2004

The Journal of Immunology

457

491

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In vitro studies have indicated the importance of Toll-like receptor (TLR) signaling in response to the fungal pathogens Candida albicans and Aspergillus fumigatus. However, the functional consequences of the complex interplay between fungal morphogenesis and TLR signaling in vivo remain largely undefined. In this study we evaluate the impact of the IL-1R/TLR/myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway on the innate and adaptive Th immunities to C. albicans and A. fumigatus in vivo. It was found that 1) the MyD88-dependent pathway is required for resistance to both fungi; 2) the involvement of the MyD88 adapter may occur through signaling by distinct members of the IL-1R/TLR superfamily, including IL-1R, TLR2, TLR4, and TLR9, with the proportional role of the individual receptors varying depending on fungal species, fungal morphotypes, and route of infection; 3) individual TLRs and IL-1R activate specialized antifungal effector functions on neutrophils, which correlates with susceptibility to infection; and 4) MyD88-dependent signaling on dendritic cells is crucial for priming antifungal Th1 responses. Thus, the finding that the innate and adaptive immunities to C. albicans and A. fumigatus require the coordinated action of distinct members of the IL-1R/TLR superfamily acting through MyD88 makes TLR manipulation amenable to the induction of host resistance to fungi.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Contribution of the Toll-Like/IL-1 Receptor Superfamily to Innate and Adaptive Immunity to Fungal Pathogens In Vivo

Bellocchio

Montagnoli

Bozza

et al. 2004

The Journal of Immunology

457

491

View full text Add to dashboard Cite

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“…26 Recognition of a single ligand has been demonstrated for TLR3 (polyI:C, representative of viral double-stranded RNA 27 ), TLR5 (bacterial flagellin 28 46 the fusion protein of respiratory syncytical virus (RSV), 47 as well as fungal ligands. 48,49 Recently, TLR7 and TLR8 were reported to recognize small imidazoquinoline compounds that have antiviral properties, 50,51 while a ligand for TLR10 has not yet been identified. Experimental confirmation of the role of the TLR family in host defense against microbes bearing one or more of these PAMPs has been obtained through the use of mice bearing spontaneous or genetically engineered defects of various TLR signaling components; these studies are summarized in the following section (see Table 2).…”

Section: Mammalian Tlrsmentioning

confidence: 99%

Toll-like receptors and their role in experimental models of microbial infection

2003

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Effective host defense against microbial infection depends upon prompt recognition of pathogens, activation of immediate containment measures, and ultimately the generation of a specific and definitive adaptive immune response. The innate immune system of the host is responsible for providing constant surveillance against infection; when confronted by pathogens it deploys a series of rapidly acting antimicrobial effectors while simultaneously instructing the adaptive immune system as to the nature and context of the infectious threat. Pathogen recognition and activation of innate immunity is mediated by members of the Toll-like receptor (TLR) family through detection of conserved microbial structures that are absent from the host. Experimental models of infection using TLR-deficient mice, as well as limited human studies, have clearly demonstrated the critical role of TLRs in host defense against most major groups of mammalian pathogens.

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“…TLRs are the most important class of pattern recognition receptors, and TLR-4 recognizes LPS from gram-negative bacteria (including Salmonella species) (5), components of M tuberculosis (6), C albicans (7), and A fumigatus (8). In critically ill patients, TLR-4 mutations resulting in hyporesponsiveness to LPS are associated with an increased incidence of gram-negative infections (14,15).…”

Section: Discussionmentioning

confidence: 99%

“…We therefore hypothesized that TNF neutralization with monoclonal antibodies may result in a decreased production of IFN␥, subsequently leading to a defective cellular immune response. In addition, both TNF and IFN␥ are known to potentiate the expression of Toll-like receptor 4 (TLR-4) on the cell membrane (3,4), and TLR-4 is important for the recognition of Salmonella species (5), Mycobacterium tuberculosis (6), C albicans (7), and A fumigatus (8) by host cells such as dendritic cells and macrophages. We therefore also assessed the impact of TNF blockade on the expression of TLR-4 on dendritic cells.…”

mentioning

confidence: 99%

Salmonella septicemia in rheumatoid arthritis patients receiving anti–tumor necrosis factor therapy: Association with decreased interferon‐γ production and toll‐like receptor 4 expression

Netea¹,

Radstake²,

Joosten³

et al. 2003

Arthritis & Rheumatism

106

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ObjectivePatients treated with antibodies to tumor necrosis factor α (TNFα) have an increased susceptibility to intracellular infections. We describe 2 patients with rheumatoid arthritis (RA) who developed Salmonella septicemia during anti‐TNF treatment. The aim of this study was to identify the mechanisms involved in the increased susceptibility of anti‐TNF–treated patients to intracellular microorganisms.MethodsWe evaluated an additional 6 RA patients receiving anti‐TNF antibodies, 5 RA patients not receiving anti‐TNF therapy, and 6 age‐ and sex‐matched healthy volunteers. The in vitro production of cytokines (interleukin‐1β [IL‐1β], IL‐6, interferon‐γ [IFNγ], and IL‐10) upon bacterial stimulation of whole blood and the expression of Toll‐like receptor 4 (TLR‐4) on dendritic cells from RA patients treated with infliximab, RA patients not treated with infliximab, and healthy controls were compared.ResultsStimulation with heat‐killed Salmonella typhimurium or Candida albicans led to a significantly decreased production of IFNγ, but not to a decreased production of IL‐10, IL‐β, or IL‐6, in anti‐TNF–treated RA patients compared with RA patients who were not receiving anti‐TNF antibodies and compared with healthy controls. TNF‐blocking treatment ex vivo significantly inhibited TLR‐4 expression on dendritic cells from RA patients and healthy controls.ConclusionSince recognition of microorganisms by TLR‐4 and activation of phagocytes by IFNγ are essential mechanisms for the defense against intracellular and fungal pathogens, we propose that this pathway is crucial for the increased susceptibility to these microorganisms in patients receiving anti‐TNF therapy.

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Involvement of CD14 and Toll-Like Receptors in Activation of Human Monocytes byAspergillus fumigatusHyphae

Cited by 211 publications

References 39 publications

The Contribution of the Toll-Like/IL-1 Receptor Superfamily to Innate and Adaptive Immunity to Fungal Pathogens In Vivo

The Contribution of the Toll-Like/IL-1 Receptor Superfamily to Innate and Adaptive Immunity to Fungal Pathogens In Vivo

Toll-like receptors and their role in experimental models of microbial infection

Salmonella septicemia in rheumatoid arthritis patients receiving anti–tumor necrosis factor therapy: Association with decreased interferon‐γ production and toll‐like receptor 4 expression

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