Antifungal Innate Immunity: A Perspective from the Last 10 Years

Salazar, Fabián; Brown, Gordon D.

doi:10.1159/000488539

Cited by 81 publications

(89 citation statements)

References 176 publications

(241 reference statements)

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“…The recognition and elimination of fungal pathogens depend of several cells of the innate immune system ( 32 ), and the importance of macrophages in combating fungal infections has been widely demonstrated. Moreover, the switching of the macrophage activation phenotype between M1 and M2 is known to be crucial for the effective control of several fungal pathogens ( 32 ). We demonstrated that BMDMs and keratinocytes released proinflammatory mediators in response to EV stimulation, which could contribute to the development of M1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions

et al. 2018

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The release of biomolecules critically affects all pathogens and their establishment of diseases. For the export of several biomolecules in diverse species, the use of extracellular vesicles (EVs) is considered to represent an alternative transport mechanism, but no study to date has investigated EVs from dermatophytes. Here, we describe biologically active EVs from the dermatophyte Trichophyton interdigitale, a causative agent of mycoses worldwide. EV preparations from T. interdigitale were examined using nanoparticle-tracking analysis, which revealed vesicular structures 20–380 nm in diameter. These vesicles induced the production of proinflammatory mediators by bone marrow-derived macrophages (BMDMs) and keratinocytes in a dose-dependent manner, and an addition of the EVs to BMDMs also stimulated the transcription of the M1-polarization marker iNOS (inducible nitric oxide synthase) and diminished the expression of the M2 markers arginase-1 and Ym-1. The observed M1 macrophages' polarization triggered by EVs was abolished in cells obtained from knockout Toll-like receptor-2 mice. Also, the EVs-induced productions of pro-inflammatory mediators were blocked too. Furthermore, the EVs from T. interdigitale enhanced the fungicidal activity of BMDMs. These results suggest that EVs from T. interdigitale can modulate the innate immune response of the host and influence the interaction between T. interdigitale and host immune cells. Our findings thus open new areas of investigation into the host-parasite relationship in dermatophytosis.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions

et al. 2018

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“…Although the phenotypic variations and activation of microglial cells are complicated, they are mainly said to be involved in anti-inflammatory and/or proinflammatory processes, depending on the infectious stimuli, and get polarized into multiple phenotypes or switch activity states [45]. Humans with a MyD88 signaling defect do not have a higher susceptibility to fungal infections [46]. However, TLR polymorphisms alters signaling pathways, thereby increasing the risk of fungal infections [47].…”

Section: Discussionmentioning

confidence: 99%

Microglial Response to Aspergillus flavus and Candida albicans: Implications in Endophthalmitis

Gandhi

Naik

Kaur

et al. 2020

JoF

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Aspergillus flavus is the most common etiology of fungal endophthalmitis in India, while Candida albicans is the causative agent in the West. In this study, we determined the role of microglial cells in evoking an inflammatory response following an infection with A. flavus and C. albicans strains isolated from patients with endophthalmitis. Microglia (CHME-3) cells were infected with A. flavus and C. albicans and the expression of Toll-Like Receptors (TLRs), cytokines and Matrix metalloproteinases (MMPs) were assessed at various time intervals. A. flavus infected cells induced higher expressions of TLR-1, -2, -5, -6, -7 and -9 and cytokines such as IL-1α, IL-6, IL-8, IL-10 and IL-17. In contrast, C. albicans infected microglia induced only TLR-2 along with the downregulation of IL-10 and IL-17. The expression of MMP-9 (Matrix metalloproteinase-9) was however upregulated in both A. flavus and C. albicans infected microglia. These results indicate that microglial cells have the ability to incite an innate response towards endophthalmitis causing fungal pathogens via TLRs and inflammatory mediators. Moreover, our study highlights the differential responses of microglia towards yeast vs. filamentous fungi.

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“…The recognition of fungi by phagocytic cells occurs mainly through the detection of cell wall components such as mannan, β-glucan, phosphocholine, β-1,6 glucan, and even internal components such as DNA can be recognized [58,59]. The recruitment and activation of phagocytic cells are mediated through the induction of proinflammatory cytokines, chemokines, and complement components.…”

Section: Cytokine Profile In Fungal Infectionsmentioning

confidence: 99%

Cytokine Profiling Plays a Crucial Role in Activating Immune System to Clear Infectious Pathogens

Muñoz‐Carrillo¹,

Contreras-Cordero²,

Gutiérrez-Coronado³

et al. 2019

Immune Response Activation and Immunomodulation

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Pathogen infections are recognized by the immune system, which consists of two types of responses: an innate immune response that recognizes pathogenassociated molecular patterns (PAMPs) and an antigen-specific adaptive immune response. In both responses, there are several activated cells of the immune system, which play a key role in establishing the environment of cytokines, thus directing their differentiation either suppressing or promoting the immune response. This immune response is crucial against pathogen infections. In this chapter, we will describe the crucial role played by different families of cytokines during activation of the immune system to eliminate infectious pathogens.

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Antifungal Innate Immunity: A Perspective from the Last 10 Years

Cited by 81 publications

References 176 publications

Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions

Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions

Microglial Response to Aspergillus flavus and Candida albicans: Implications in Endophthalmitis

Cytokine Profiling Plays a Crucial Role in Activating Immune System to Clear Infectious Pathogens

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