Cytoskeletal Alteration Is an Early Cellular Response in Pulmonary Epithelium Infected with Aspergillus fumigatus Rather than Scedosporium apiospermum

Kanjanapruthipong, Tapanee; Sukphopetch, Passanesh; Reamtong, Onrapak; Isarangkul, Duangnate; Muangkaew, Watcharamat; Thiangtrongjit, Tipparat; Sansurin, Nichapa; Fongsodsri, Kamonpan; Ampawong, Sumate

doi:10.1007/s00248-021-01750-7

Cited by 7 publications

(6 citation statements)

References 101 publications

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“…Further analyses revealed that a dysfunctional cytoskeleton may account for the high prevalence of CM in patients with HIV/AIDS. Studies indicated a similar variation of cytoskeleton pathway during HIV infection and C. neoformans or A. fumigates infections [ 23 , 42 , 43 , 47 , 48 ]. Indeed, C. neoformans is an environmental yeast that is globally ubiquitous and easily accessible for all individuals [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain

Han

et al. 2022

Emerging Microbes & Infections

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Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ARTnaive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans . Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage “Trojan Horse” in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC , was found to be a novel enhancer for the macrophage “Trojan Horse,” and an enhanced fungal burden was achieved in the brains of MYOC -transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

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Section: Discussionmentioning

confidence: 99%

Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain

Han

et al. 2022

Emerging Microbes & Infections

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“…Our studies illustrated the basic functions of cytoskeleton dynamics on phagocytosis, migration and killing of macrophages, which are vital for eliminating, blocking fungal cells or fungal cell intracellular proliferation and vomocytosis[49]. Inhibitors of cytoskeleton pathways were efficient for blocking fungal cells from the brain in the early stage of meningitis, however, reciprocal in late stage, these were different phenotypes from “Trojan horse”, which may result from cytoskeletal alteration participates early cellular responses in fungal infections[47]. Furthermore, this phenomenon indicated the toxic of the small molecule drugs, such as vanadate, cytochalasin D, Y27632 and R10015[30, 38, 50], which involves fundamental roles of innate immunity and acquired immunity of macrophages, NK cell and T cells, who also play important roles during fungal, bacterial and virus infections.…”

Section: Discussionmentioning

confidence: 99%

“…Our data identified the fundamental roles of cytoskeleton during “Trojan Horse” formation. Studies have indicated the relationship between cytoskeleton and fungal infections[30, 31, 36, 46, 47]. Previous studies highlighted important roles of “Trojan horse” by macrophages during fungal CNS invasion, the processes of which require viability and cellular deformation, and these are cytoskeleton dependent.…”

Section: Discussionmentioning

confidence: 99%

“…Further analyses revealed that dysfunctional cytoskeleton may account for the high prevalence of cryptococcal meningitis in HIV/AIDS patients. Studies indicated a similar variation of cytoskeleton pathway during HIV infection and C. neoformans or A. fumigates infections [23,42,43,47,48]. Indeed, C. neoformans is an environmental yeast globally ubiquitous, and easily accessible for all individuals[49].…”

Section: Discussionmentioning

confidence: 99%

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Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain

Li¹,

Han²,

et al. 2022

Preprint

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Cryptococcal meningitis is a major risk for immune compromised patients mainly caused by the human opportunistic pathogen Cryptococcus neoformans, yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton was a centric pathway regulated in both two organisms. Notably, myocilin, a novel modulator encoded by MYOC, was identified during cryptococcal pneumonia. An enhanced fungal burden was achieved in the brains of MYOC transgenic mice. Importantly, C. neoformans dissemination to the brain was inhibited by cytoskeleton inhibitor, which ruined “Trojan Horse” by dampening migration and phagocytosis of macrophages, but toxic to hosts. Taking together, this study provides new pathways and modulators during C. neoformans infections and reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination that facilitate the development of novel drug targets for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.Author summaryFungal CNS dissemination is vital and lethal, which is the most important step for both fungal pathogenesis and host defense. Many milestones have been made to illustrate processes of invasion, such as the “Trojan Horse” derived by macrophages. However, blocking this “road” is still on the way. In our work, to mimic real responses in humans, macaque and mouse were included, miRNA-Seq and mRNA-Seq were combined, and we identified the core-pathway (cytoskeleton) during C. neoformans pathogenesis, which plays important roles in migration and phagocytosis for macrophages, key factors for macrophage “Trojan horse”, and cytoskeleton was also ruined in HIV/AIDS patients. Fungal brain dissemination was weakened by cytoskeleton inhibitor in mice. Meanwhile, we identified a novel modulator for macrophage “Trojan Horse”, MYOC, involved with C. neoformans brain dissemination. Consistently, we assume macrophages are the key executor cells for fungal CNS dissemination, and we propose the processes can be shut down by cytoskeleton or MYOC inhibitors. Our research would not only help to understand the high prevalence of cryptococcal meningitis in HIV/AIDS but also provides putative ways to block fungal cells invading the brain.

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“…The shared immune-related gene families included receptor-related genes from both innate and acquired immunity. The gene families associated with innated immunity included C-type lectin (Weis et al, 1998;Kanjanapruthipong et al, 2022), an important pattern recognition receptor, and butyrophilin, which is involved in T-cell gd activation (Nielsen et al, 2017;Uldrich et al, 2020). The immunoglobulin receptor, the V region of the T-cell receptor (Bassing et al, 2002), and the CD4 glycoprotein (Leahy, 1995) are all members of the acquired immunity gene families.…”

Section: Discussionmentioning

confidence: 99%

The chromosome-level genome assembly of goldstripe ponyfish (Karalla daura) reveals its similarity to Chinese sillago on contracted immune gene families

Shi

Xia

et al. 2022

Front. Mar. Sci.

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The goldstripe ponyfish is a small tropical economic fish in the Leiognathidae family. The genome of this fish was assembled as 24 chromosomes with a total length of 577.66 Mb and 54.81 Mb unanchored contigs using HiFi and Hi-C sequencing technologies. There are 256.7 Mb of repeat elements, which cover 40.59% of the genome, and 21,506 coding genes, which cover 47.68%. According to phylogenetic analysis, the goldstripe ponyfish is closely related to the Sillaginidae family’s Chinese sillago. The distance between goldstripe ponyfish and Chinese sillago in the hierarchical clustering of gene family contractions and expansions is also the shortest, indicating a similarity even greater than that between croakers of the same family (Sciaenidae). The goldstripe ponyfish and Chinese sillago share 25 identical contracted gene families, the majority of which are immune recognition receptors, such as innate immunity-related C-type lectin and butyrophilin families, as well as acquired immunity-related T-cell receptor region V and the surface glycoprotein CD4, implying that these two fishes’ immune systems may adopt similar evolutionary strategy at the genomic level. Additionally, the positively selected genes of the Chinese sillago and the goldstripe ponyfish were enriched in biological functions involved in the cell cycle, such as telomeres, which may account for the disparities in body size and lifespan between the two species.

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Cytoskeletal Alteration Is an Early Cellular Response in Pulmonary Epithelium Infected with Aspergillus fumigatus Rather than Scedosporium apiospermum

Cited by 7 publications

References 101 publications

Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain

Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain

The chromosome-level genome assembly of goldstripe ponyfish (Karalla daura) reveals its similarity to Chinese sillago on contracted immune gene families

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