Integrity under stress: Host membrane remodelling and damage by fungal pathogens

Westman, Johannes; Hube, Bernhard; Fairn, Gregory D.

doi:10.1111/cmi.13016

Cited by 28 publications

(23 citation statements)

References 84 publications

(116 reference statements)

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“…Likewise, it has been reported that the lysis of macrophages also requires live C . albicans that forms hyphae, which stress phagosomal membranes [59], disrupt the macrophages with their associated toxin [57] and compete with the host for glucose [60]. In this context, a pertinent question that comes out of these findings is whether the induced pyroptosis benefits the host, the fungus or both.…”

Section: Discussionmentioning

confidence: 99%

Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis

et al. 2019

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The granulomatous lesion resulting from infection with the fungus Paracoccidioides brasiliensis is characterized by a compact aggregate of mature cells, surrounded by a fibroblast- and collagen-rich content. Granuloma formation requires signaling elicited by inflammatory molecules such as members of the interleukin-1 family. Two members of this family have been thoroughly studied, namely IL-1α and IL-1β. In this study, we addressed the mechanisms underlying IL-1α secretion and its functional role on the host resistance to fungal infection. We found that, the expression of caspase-11 triggered by P . brasiliensis infection of macrophages depends on IFN-β production, because its inhibition reduced procaspase-11 levels. Curiously, caspase-11 deficiency did not impair IL-1β production, however caspase-11 was required for a rapid pore-mediated cell lysis. The plasma membrane rupture facilitated the release of IL-1α, which was necessary to induce NO production and restrict fungal replication. Furthermore, P . brasiliensis -infected macrophages required IL-1α to produce optimal levels of IL-6, a major component of Th17 lymphocyte differentiation. Indeed, IL-1α deficiency accounted for a significant reduction of Th17 lymphocytes in lungs of infected mice, correlating with diminished neutrophil infiltration in the lungs. Strikingly, we identified that IL-1α directly reprograms the transcriptional profile of Th17-committed lymphocytes, increasing cellular proliferation, as for boosting IL-17 production by these cells. Beyond neutrophil chemotaxis in vivo , IL-17 also amplified IL-1α production by infected macrophages in vitro , endorsing a critical amplification loop of the inflammatory response. Therefore, our data suggest that the IFN-β/caspase-11/IL-1α pathway shapes a protective antifungal Th17 immunity, revealing a molecular mechanism underlying the cross-talk between innate and adaptive immunity.

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Section: Discussionmentioning

confidence: 99%

Caspase-11-dependent IL-1α release boosts Th17 immunity against Paracoccidioides brasiliensis

et al. 2019

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“…Host defense also includes the epithelial physical barrier and host immune cells, such as macrophages. Hyphal growth is associated with mechanical forces during the interaction of C. albicans with such host cells 56 . The relative contribution of these mechanical forces to host cell damage, compared with other hyphal attributes, is an area of active investigation.…”

Section: Host Interactionsmentioning

confidence: 99%

Recent advances in understanding Candida albicans hyphal growth

Arkowitz

Bassilana

2019

F1000Res

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Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. Candida albicans is a major human fungal pathogen whose ability to switch between different morphological states is associated with its adaptability and pathogenicity. In particular, C. albicans can switch from an oval yeast form to a filamentous hyphal form, which is characteristic of filamentous fungi. What mechanisms underlie hyphal growth and how are they affected by environmental stimuli from the host or resident microbiota? These questions are the focus of intensive research, as understanding C. albicans hyphal growth has broad implications for cell biological and medical research.

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“…However, some pathogens not only survive inside phagosomes, but can grow therein (Flannagan et al, 2016;Naderer and McConville, 2011). Growth often implies replication of the pathogen, but in some instances the size of the microorganism increases (Westman et al, 2019a). The latter is the case of fungi such as Candida albicans, which undergoes a yeast-to-hyphal transition inside phagosomes (Austermeier et al, 2020).…”

Section: Introductionmentioning

confidence: 99%