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  1. Article ; Online: Immune responses to human fungal pathogens and therapeutic prospects.

    Lionakis, Michail S / Drummond, Rebecca A / Hohl, Tobias M

    Nature reviews. Immunology

    2023  Volume 23, Issue 7, Page(s) 433–452

    Abstract: Pathogenic fungi have emerged as significant causes of infectious morbidity and death in patients with acquired immunodeficiency conditions such as HIV/AIDS and following receipt of chemotherapy, immunosuppressive agents or targeted biologics for ... ...

    Abstract Pathogenic fungi have emerged as significant causes of infectious morbidity and death in patients with acquired immunodeficiency conditions such as HIV/AIDS and following receipt of chemotherapy, immunosuppressive agents or targeted biologics for neoplastic or autoimmune diseases, or transplants for end organ failure. Furthermore, in recent years, the spread of multidrug-resistant Candida auris has caused life-threatening outbreaks in health-care facilities worldwide and raised serious concerns for global public health. Rapid progress in the discovery and functional characterization of inborn errors of immunity that predispose to fungal disease and the development of clinically relevant animal models have enhanced our understanding of fungal recognition and effector pathways and adaptive immune responses. In this Review, we synthesize our current understanding of the cellular and molecular determinants of mammalian antifungal immunity, focusing on observations that show promise for informing risk stratification, prognosis, prophylaxis and therapies to combat life-threatening fungal infections in vulnerable patient populations.
    MeSH term(s) Animals ; Humans ; Mycoses/drug therapy ; Mycoses/microbiology ; Fungi ; Antifungal Agents/therapeutic use ; Immunity ; Mammals
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2023-01-04
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-022-00826-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mitochondrial Reactive Oxygen Species Enhance Alveolar Macrophage Activity against Aspergillus fumigatus but Are Dispensable for Host Protection.

    Shlezinger, Neta / Hohl, Tobias M

    mSphere

    2021  Volume 6, Issue 3, Page(s) e0026021

    Abstract: Aspergillus fumigatus is the most common cause of mold pneumonia worldwide, and a significant cause of infectious morbidity and mortality in immunocompromised individuals. The oxidative burst, which generates reactive oxidative species (ROS), plays a ... ...

    Abstract Aspergillus fumigatus is the most common cause of mold pneumonia worldwide, and a significant cause of infectious morbidity and mortality in immunocompromised individuals. The oxidative burst, which generates reactive oxidative species (ROS), plays a pivotal role in host defense against aspergillosis and induces regulated cell death in Aspergillus conidia, the infectious propagules. Beyond the well-established role of NADP (NADPH) oxidase in ROS generation by neutrophils and other innate effector cells, mitochondria represent a major ROS production site in many cell types, though it is unclear whether mitochondrial ROS (mtROS) contribute to antifungal activity in the lung. Following A. fumigatus infection, we observed that innate effector cells, including alveolar macrophages (AMs), monocyte-derived dendritic cells (Mo-DCS), and neutrophils, generated mtROS, primarily in fungus-infected cells. To examine the functional role of mtROS, specifically the H
    MeSH term(s) Animals ; Aspergillosis/immunology ; Aspergillus fumigatus/immunology ; Aspergillus fumigatus/pathogenicity ; Host-Pathogen Interactions/immunology ; Hydrogen Peroxide/metabolism ; Immunity, Innate ; Lung/immunology ; Lung/microbiology ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondria/immunology ; Mitochondria/metabolism ; Reactive Oxygen Species/immunology
    Chemical Substances Reactive Oxygen Species ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/mSphere.00260-21
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  3. Article: Dectin-1/CARD9-induction of the TFEB and TFE3 gene network is dispensable for phagocyte anti-

    Aufiero, Mariano A / Shlezinger, Neta / Gjonbalaj, Mergim / Mills, Kathleen A M / Ballabio, Andrea / Hohl, Tobias M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Myeloid phagocytes of the respiratory immune system, such as neutrophils, monocytes, and alveolar macrophages, are essential for immunity ... ...

    Abstract Myeloid phagocytes of the respiratory immune system, such as neutrophils, monocytes, and alveolar macrophages, are essential for immunity to
    Language English
    Publishing date 2023-06-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.13.544785
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  4. Article ; Online: Call to Action: How to Tackle Emerging Nosocomial Fungal Infections.

    Lionakis, Michail S / Hohl, Tobias M

    Cell host & microbe

    2020  Volume 27, Issue 6, Page(s) 859–862

    Abstract: Nosocomial fungal infections require a robust scientific response to complement antifungal development and the implementation of infection control measures. This Commentary discusses how a parallel effort to address fungal pathogenesis and antifungal ... ...

    Abstract Nosocomial fungal infections require a robust scientific response to complement antifungal development and the implementation of infection control measures. This Commentary discusses how a parallel effort to address fungal pathogenesis and antifungal immunity, the mycobiota and colonization resistance, and risk factors is essential to reduce the toll of these infections.
    MeSH term(s) Antifungal Agents/immunology ; Antifungal Agents/therapeutic use ; Cross Infection/drug therapy ; Cross Infection/immunology ; Cross Infection/microbiology ; Fungi/pathogenicity ; Humans ; Immunity ; Mycobiome/drug effects ; Mycobiome/immunology ; Mycoses/microbiology ; Risk Factors
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2020-06-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2020.04.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Fungal Infections Associated With the Use of Novel Immunotherapeutic Agents.

    Bernardes, Marilia / Hohl, Tobias M

    Current clinical microbiology reports

    2020  Volume 7, Issue 4, Page(s) 142–149

    Abstract: Purpose of the review: Recent concerns have emerged regarding the potential of immunotherapy to cause infection. In this review, we summarize the current literature on invasive fungal infections that occur during treatment with immune checkpoint ... ...

    Abstract Purpose of the review: Recent concerns have emerged regarding the potential of immunotherapy to cause infection. In this review, we summarize the current literature on invasive fungal infections that occur during treatment with immune checkpoint inhibitors and chimeric antigen receptor T cell therapy.
    Recent findings: Fungal infections are uncommon with the use of checkpoint inhibitors. Most cases are caused by invasive aspergillosis and pneumocystis pneumonia and occur in patients requiring high dose corticosteroids for the management of immune-related adverse events. Conversely, fungal infections are commonly reported during therapy with CAR T cells. Most cases are caused by invasive aspergillosis and candidiasis and are likely the result of prolonged neutropenia following the conditioning regimen or immunosuppressant use for the management of cytokine release syndrome and neurotoxicity.
    Summary: Treatment-related toxicities that require prolonged immunosuppressive agents appear to play a key role in the development of fungal infections during immunotherapy. Ongoing surveillance is needed to fully address the risks of fungal infections with these novel agents.
    Language English
    Publishing date 2020-09-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2786543-5
    ISSN 2196-5471
    ISSN 2196-5471
    DOI 10.1007/s40588-020-00154-4
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  6. Article ; Online: Immune responses to invasive aspergillosis: new understanding and therapeutic opportunities.

    Hohl, Tobias M

    Current opinion in infectious diseases

    2017  Volume 30, Issue 4, Page(s) 364–371

    Abstract: Purpose of review: Invasive aspergillosis is a worldwide disease that primarily affects immune-compromised patients, agricultural workers with corneal abrasions, individuals with structural lung disease, and patients with primary immune deficiency. The ... ...

    Abstract Purpose of review: Invasive aspergillosis is a worldwide disease that primarily affects immune-compromised patients, agricultural workers with corneal abrasions, individuals with structural lung disease, and patients with primary immune deficiency. The critical function of the immune system is to prevent the germination of airborne conidia into tissue-invasive hyphae. This review covers recent advances that shape our understanding of anti-Aspergillus immunity at the molecular and cellular level.
    Recent findings: Host defense against conidia and hyphae occurs via distinct molecular mechanisms that involve intracellular and extracellular killing pathways, as well as cooperation between different myeloid cell subsets. The strength and efficacy of the host response is shaped by the tissue microenvironment. In preclinical models of disease, host immune augmentation strategies have yielded benefits, yet translating these insights into therapeutic strategies in humans remains challenging.
    Summary: Although advances in early diagnostic strategies and in antifungal drugs have ameliorated clinical outcomes of invasive aspergillosis, further improvements depend on gaining deeper insight into and translating advances in anti-Aspergillus immunity.
    MeSH term(s) Agricultural Workers' Diseases/microbiology ; Antifungal Agents/therapeutic use ; Aspergillosis/immunology ; Aspergillus/immunology ; Humans ; Immunity, Cellular ; Immunity, Innate ; Immunocompromised Host
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2017-04-27
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 645085-4
    ISSN 1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
    ISSN (online) 1473-6527 ; 1535-3877
    ISSN 0951-7375 ; 1355-834X
    DOI 10.1097/QCO.0000000000000381
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    Zs.A 2462: Show issues Location:
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  7. Article ; Online: Dectin-1/CARD9 induction of the TFEB and TFE3 gene network is dispensable for phagocyte anti-

    Aufiero, Mariano A / Shlezinger, Neta / Gjonbalaj, Mergim / Mills, Kathleen A M / Ballabio, Andrea / Hohl, Tobias M

    Infection and immunity

    2023  Volume 91, Issue 11, Page(s) e0021723

    Abstract: Myeloid phagocytes of the respiratory immune system, such as neutrophils, monocytes, and alveolar macrophages, are essential for immunity ... ...

    Abstract Myeloid phagocytes of the respiratory immune system, such as neutrophils, monocytes, and alveolar macrophages, are essential for immunity to
    MeSH term(s) Animals ; Mice ; Aspergillosis ; Aspergillus fumigatus ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Gene Regulatory Networks ; Lung ; Phagocytes ; Pneumonia
    Chemical Substances Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; dectin 1 ; Card9 protein, mouse ; Tcfeb protein, mouse ; Tcfe3 protein, mouse (136896-33-8)
    Language English
    Publishing date 2023-10-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00217-23
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    Zs.A 684: Show issues Location:
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  8. Article ; Online: Mycobiota dysbiosis and gastric tumorigenesis.

    Papon, Nicolas / Hohl, Tobias M / Zhai, Bing

    Theranostics

    2021  Volume 11, Issue 15, Page(s) 7488–7490

    Abstract: The gastrointestinal tract contains a vast and diverse microbial reservoir composed of bacteria, fungi, and viruses that contribute positively to human health. There is growing evidence that perturbation of the normal microbiota can promote a variety of ... ...

    Abstract The gastrointestinal tract contains a vast and diverse microbial reservoir composed of bacteria, fungi, and viruses that contribute positively to human health. There is growing evidence that perturbation of the normal microbiota can promote a variety of human disease states that include tumorigenesis. Whether the fungal component of the gut microbiota (i.e., the mycobiota) can influence tumor development has not been investigated in detail. In the recent issue of the
    MeSH term(s) Carcinogenesis ; Dysbiosis/microbiology ; Gastrointestinal Microbiome ; Humans ; Stomach Neoplasms/microbiology
    Language English
    Publishing date 2021-06-01
    Publishing country Australia
    Document type Editorial
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.61480
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  9. Article ; Online: Exploring Candida auris in its habitat.

    Zhai, Bing / Rolling, Thierry / Hohl, Tobias M

    Cell host & microbe

    2021  Volume 29, Issue 2, Page(s) 150–151

    Abstract: Candida auris colonizes human skin and causes life-threatening fungal bloodstream infections. In this issue of Cell Host & Microbe, Huang et al. introduce a murine model of C. auris skin colonization to explore the role of distinct clades, immune ... ...

    Abstract Candida auris colonizes human skin and causes life-threatening fungal bloodstream infections. In this issue of Cell Host & Microbe, Huang et al. introduce a murine model of C. auris skin colonization to explore the role of distinct clades, immune signaling pathways, antibiotics, and disinfectants on fungal persistence in or clearance from its habitat.
    MeSH term(s) Animals ; Candida ; Disease Models, Animal ; Ecosystem ; Humans ; Mice ; Risk Factors ; Viral Tropism
    Language English
    Publishing date 2021-02-10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2021.01.010
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  10. Article ; Online: Immunity to fungi in the lung.

    Heung, Lena J / Wiesner, Darin L / Wang, Keyi / Rivera, Amariliz / Hohl, Tobias M

    Seminars in immunology

    2023  Volume 66, Page(s) 101728

    Abstract: The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, ... ...

    Abstract The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.
    MeSH term(s) Humans ; COVID-19 ; Mycoses ; Lung ; Fungi ; Immunity, Innate
    Language English
    Publishing date 2023-02-24
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2023.101728
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