The impact of episporic modification of Lichtheimia corymbifera on virulence and interaction with phagocytes

Hassan, Mohamed I. Abdelwahab; Keller, Monique; Hillger, Michael; Binder, Ulrike; Reuter, Stefanie; Herold, Kristina; Telagathoti, Anusha; Dahse, Hans‐Martin; Wicht, Saiedeh; Trinks, Nora; Nietzsche, Sándor; Deckert‐Gaudig, Tanja; Deckert, Volker; Mrowka, Ralf; Terpitz, Ulrich; Saluz, Hans Peter; Voigt, Kerstin

doi:10.1016/j.csbj.2021.01.023

Cited by 7 publications

(8 citation statements)

References 54 publications

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“…albicans have developed different strategies to evade immune detection either via modification in their cell-wall constituents or secretion of inhibitory fungal molecules ( 28 , 40 , 55 – 59 ). In contrast to the previous pathogenic fungi, the most virulent strain of L. corymbifera (FSU: 009682) did not exhibit avoidance of immune detection by monocytes and neutrophils since its sporangiospores were rapidly and efficiently phagocytized by both cell types ( Figure 1A ), which suggests the presence of highly immunogenic molecules in its cell wall, such as β-1,3-glucans, as shown in L. corymbifera germlings ( Figure S5 ), or unmasked chitosan after removal of glucans ( 60 ). However, recognition of an attenuated strain of L. corymbifera (FSU:10164) was reduced approximately by half when compared to the virulent strain ( Figure S1B ), indicating possible differences in the cell wall composition of each strain, which could influence on their virulence.…”

Section: Discussionmentioning

confidence: 99%

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis

Montaño

Hartung²,

Wich³

et al. 2022

Front. Immunol.

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Invasive mucormycosis (IM) is a life-threatening infection caused by the fungal order Mucorales, its diagnosis is often delayed, and mortality rates range from 40-80% due to its rapid progression. Individuals suffering from hematological malignancies, diabetes mellitus, organ transplantations, and most recently COVID-19 are particularly susceptible to infection by Mucorales. Given the increase in the occurrence of these diseases, mucormycosis has emerged as one of the most common fungal infections in the last years. However, little is known about the host immune response to Mucorales. Therefore, we characterized the interaction among L. corymbifera—one of the most common causative agents of IM—and human monocytes, which are specialized phagocytes that play an instrumental role in the modulation of the inflammatory response against several pathogenic fungi. This study covered four relevant aspects of the host-pathogen interaction: i) The recognition of L. corymbifera by human monocytes. ii) The intracellular fate of L. corymbifera. iii) The inflammatory response by human monocytes against the most common causative agents of mucormycosis. iv) The main activated Pattern-Recognition Receptors (PRRs) inflammatory signaling cascades in response to L. corymbifera. Here, we demonstrate that L. corymbifera exhibits resistance to intracellular killing over 24 hours, does not germinate, and inflicts minimal damage to the host cell. Nonetheless, viable fungal spores of L. corymbifera induced early production of the pro-inflammatory cytokine IL-1β, and late release of TNF-α and IL-6 by human monocytes. Moreover, we revealed that IL-1β production predominantly depends on Toll-like receptors (TLRs) priming, especially via TLR4, while TNF-α is secreted via C-type lectin receptors (CTLs), and IL-6 is produced by synergistic activation of TLRs and CTLs. All these signaling pathways lead to the activation of NF-kB, a transcription factor that not only regulates the inflammatory response but also the apoptotic fate of monocytes during infection with L. corymbifera. Collectively, our findings provide new insights into the host-pathogen interactions, which may serve for future therapies to enhance the host inflammatory response to L. corymbifera.

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Section: Discussionmentioning

confidence: 99%

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis

Montaño

Hartung²,

Wich³

et al. 2022

Front. Immunol.

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“…For this extended intracellular concealment, it applies several strategies, including melanization and metabolic adaptation, and inhibits the host cell apoptosis of polymorphonuclear cells by inducing autocrine IL‐8 production (Acorci et al, 2009). Furthermore, it has been shown that the resting conidia of A. fumigatus and Mucorales species can inhibit apoptosis of macrophages as well (Andrianaki et al, 2018; Hassan et al, 2021; Volling et al, 2011), securing their extended intracellular phase.…”

Section: Persistencementioning

confidence: 99%

“We've got to get out”—Strategies of human pathogenic fungi to escape from phagocytes

Sonnberger,

Kasper,

Lange

et al. 2023

Molecular Microbiology

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Human fungal pathogens are a deadly and underappreciated risk to global health that most severely affect immunocompromised individuals. A virulence attribute shared by some of the most clinically relevant fungal species is their ability to survive inside macrophages and escape from these immune cells. In this review, we discuss the mechanisms behind intracellular survival and elaborate how escape is mediated by lytic and non‐lytic pathways as well as strategies to induce programmed host cell death. We also discuss persistence as an alternative to rapid host cell exit. In the end, we address the consequences of fungal escape for the host immune response and provide future perspectives for research and development of targeted therapies.

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“…In addition, both genera induce phagosome maturation arrest mediated by cell wall melanin and the calcineurin signal pathway in Rhizopus ( Andrianaki et al., 2018 ) and Mucor species ( Lee et al., 2015 ; Vellanki et al., 2020 ), respectively. Resting spores of Lichtheimia corymbifera also inhibits the intracellular acidification of macrophages in vitro , independently from melanin ( Hassan et al., 2021 ).…”

Section: Understanding the Fungal Response To The Macrophage Attackmentioning

confidence: 99%

Recent Advances and Future Directions in the Understanding of Mucormycosis

Garre

2022

Front. Cell. Infect. Microbiol.

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Mucormycosis is an emerging infection caused by fungi of the order Mucorales that has recently gained public relevance due to the high incidence among COVID-19 patients in some countries. The reduced knowledge about Mucorales pathogenesis is due, in large part, to the historically low interest for these fungi fostered by their reluctance to be genetically manipulated. The recent introduction of more tractable genetic models together with an increasing number of available whole genome sequences and genomic analyses have improved our understanding of Mucorales biology and mucormycosis in the last ten years. This review summarizes the most significant advances in diagnosis, understanding of the innate and acquired resistance to antifungals, identification of new virulence factors and molecular mechanisms involved in the infection. The increased awareness about the disease and the recent successful genetic manipulation of previous intractable fungal models using CRISPR-Cas9 technology are expected to fuel the characterization of Mucorales pathogenesis, facilitating the development of effective treatments to fight this deadly infection.

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The impact of episporic modification of Lichtheimia corymbifera on virulence and interaction with phagocytes

Abstract: Graphical abstract

Cited by 7 publications

References 54 publications

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis

“We've got to get out”—Strategies of human pathogenic fungi to escape from phagocytes

Recent Advances and Future Directions in the Understanding of Mucormycosis

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