PAMPs of the Fungal Cell Wall and Mammalian PRRs

Hatinguais, Remi; Willment, Janet A.; Brown, Gordon D.

doi:10.1007/82_2020_201

Cited by 38 publications

(58 citation statements)

References 232 publications

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“…The essential role of TLR-2 and TLR-4 in the recognition of Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans antigens was reported [27]. Over the last two decades, the contributions to the literature of TLR interactions with various fungi were extremely rich, and expertly reviewed by some authors which are important contributions to the field [28][29][30].…”

Section: Cells Of the Innate Immunitymentioning

confidence: 99%

Paracoccidioidomycosis Protective Immunity

Burger

2021

JoF

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Protective immunity against Paracoccidioides consists of a stepwise activation of numerous effector mechanisms that comprise many cellular and soluble components. At the initial phase of non-specific innate immunity, resistance against Paracoccidioides comes from phagocytic polymorphonuclear neutrophils, natural killer (NK) cells and monocytes, supplemented by soluble factors such as cytokines and complement system components. Invariant receptors (Toll-like receptors (TLRs), Dectins) which are present in cells of the immune system, detect patterns present in Paracoccidioides (but not in the host) informing the hosts cells that there is an infection in progress, and that the acquired immunity must be activated. The role of components involved in the innate immunity of paracoccidioidomycosis is herein presented. Humoral immunity, represented by specific antibodies which control the fungi in the blood and body fluids, and its role in paracoccidioidomycosis (which was previously considered controversial) is also discussed. The protective mechanisms (involving various components) of cellular immunity are also discussed, covering topics such as: lysis by activated macrophages and cytotoxic T lymphocytes, the participation of lytic products, and the role of cytokines secreted by T helper lymphocytes in increasing the efficiency of Paracoccidioides, lysis.

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Section: Cells Of the Innate Immunitymentioning

confidence: 99%

Paracoccidioidomycosis Protective Immunity

Burger

2021

JoF

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“…Detection of fungal pathogens by the host immune system occurs mainly through recognition of the fungal cell wall that includes multiple pathogen‐associated molecular patterns (PAMPs) 10 . The fungal cell wall is composed of various polysaccharides and glycoproteins, forming a structure that is essential for fungal viability and confers protection against environmental stress 11,12 .…”

Section: Fungal Pathogen‐associated Molecular Patternsmentioning

confidence: 99%

“…Similarly, several PRRs including mannose receptor (MR) as well as toll‐like receptor (TLR)‐2 and ‐9 are known to recognize chitin, the other major component of the inner fungal cell wall 16,17 . The various O‐linked and N‐linked mannosylated glycoproteins constitute the main PAMPs of the outer fungal cell wall and are recognized by the vast repertoire of PRRs such as TLR‐2, TLR‐4, dectin‐2, CD209 and MR (reviewed in Ref 10…”

Section: Fungal Pathogen‐associated Molecular Patternsmentioning

confidence: 99%

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Fungal recognition by mammalian fibrinogen‐related proteins

Pilecki

Møeller

2020

Scand J Immunol

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Fungi are ubiquitous eukaryotic microorganisms present in virtually all environmental habitats. Although rarely pathogenic to the healthy population, many fungal species are capable of causing human disease in immunocompromised individuals. Thus, fungal infections remain a significant cause of morbidity and mortality, with rising prevalence accompanying the worldwide increase in immunosuppressionbased therapies. Therefore, better understanding of the mutual interactions between the protective host mechanisms and the invading fungi remains of critical importance. The innate immune system constitutes the first line of defence against exogenous insults. The innate antifungal immunity is mediated through recognition of specific pathogen-associated molecular patterns (PAMPs) by a broad panel of host pattern recognition receptors (PRRs), responsible for mounting adequate protective responses. In this review, we describe fungal PAMPs as well as a selection of PRRs able to recognize them. We focus on the members of the fibrinogen-related domain (FReD) protein family that have been shown to recognize fungi-derived molecules: ficolins, fibrinogen C domain containing 1 (FIBCD1) and tenascin-C. We describe their structure, their binding targets and their established as well as putative biological functions related to fungal recognition and immunity. F I G U R E 1 The fungal cell wall and exposure of PAMPs during fungal cell transitions. A, Schematic representation of the fungal cell wall. The outer cell wall primarily composed of mannoproteins (blue) shields the inner cell wall composed of glucans (red) and chitin (yellow) from recognition by host immunity. B, Schematic representation of fungal yeast cell division. During fungal cell division and in budding scars after division, the inner cell wall components (glucans and chitin) are exposed to the environment and can be recognized by the host. C, Representation of conidia, germination and growth of germ tubes. During germination (swollen conidia) and formation of germ tubes, the inner cell wall components are exposed to the environment and can be recognized by the host. D, Schematic representation of filamentous growth of hyphaeforming fungi. During formation and growth of hyphae, the inner cell wall components may be exposed to the environment and potentially recognized by the host How to cite this article: Pilecki B, Moeller JB. Fungal recognition by mammalian fibrinogen-related proteins.

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“…The recognition of microbial ligands by various receptors is required to initiate immune responses and antimicrobial signalling ( 45 ). Currently, little is known about the ligands that induce inflammatory responses through RET-associated mitoROS signalling.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Reactive Oxygen Species Regulate Immune Responses of Macrophages to Aspergillus fumigatus

et al. 2021

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Reactive Oxygen Species (ROS) are highly reactive molecules that can induce oxidative stress. For instance, the oxidative burst of immune cells is well known for its ability to inhibit the growth of invading pathogens. However, ROS also mediate redox signalling, which is important for the regulation of antimicrobial immunity. Here, we report a crucial role of mitochondrial ROS (mitoROS) in antifungal responses of macrophages. We show that mitoROS production rises in murine macrophages exposed to swollen conidia of the fungal pathogen Aspergillus fumigatus compared to untreated macrophages, or those treated with resting conidia. Furthermore, the exposure of macrophages to swollen conidia increases the activity of complex II of the respiratory chain and raises mitochondrial membrane potential. These alterations in mitochondria of infected macrophages suggest that mitoROS are produced via reverse electron transport (RET). Significantly, preventing mitoROS generation via RET by treatment with rotenone, or a suppressor of site IQ electron leak, S1QEL1.1, lowers the production of pro-inflammatory cytokines TNF-α and IL-1β in macrophages exposed to swollen conidia of A. fumigatus. Rotenone and S1QEL1.1 also reduces the fungicidal activity of macrophages against swollen conidia. Moreover, we have established that elevated recruitment of NADPH oxidase 2 (NOX2, also called gp91phox) to the phagosomal membrane occurs prior to the increase in mitoROS generation. Using macrophages from gp91phox-/- mice, we have further demonstrated that NOX2 is required to regulate cytokine secretion by RET-associated mitoROS in response to infection with swollen conidia. Taken together, these observations demonstrate the importance of RET-mediated mitoROS production in macrophages infected with A. fumigatus.

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PAMPs of the Fungal Cell Wall and Mammalian PRRs

Cited by 38 publications

References 232 publications

Paracoccidioidomycosis Protective Immunity

Paracoccidioidomycosis Protective Immunity

Fungal recognition by mammalian fibrinogen‐related proteins

Mitochondrial Reactive Oxygen Species Regulate Immune Responses of Macrophages to Aspergillus fumigatus

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