Article
Immunology
Ya-li Yang, Yi-bin Fan, Lei Gao, Chao Zhang, Ju-lin Gu, Wei-hua Pan, Wei Fang
Summary: This study elucidates the role of Csn1201 protein in cryptococcal fitness and host immunity. Deletion of Csn1201 blocks the pulmonary infection and extrapulmonary dissemination of Cryptococcus neoformans, while enhancing the host immune response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Thitinan Kitisin, Watcharamat Muangkaew, Passanesh Sukphopetch
Summary: This study revealed a relationship between longevity and immunity in the context of cryptococcal infections. The defects in the C. elegans insulin/IGF-1 signaling pathway influenced animal lifespan and host resistance mechanisms, with the activation of the aging regulator DAF-16/Forkhead box O transcription factor playing a crucial role. Host defenses during cryptococcal infections led to increased accumulation of lipofuscin, DAF-16 nuclear localization, and expression of superoxide dismutase (SOD-3) in C. elegans.
Article
Public, Environmental & Occupational Health
Yingyu Zhang, Weiliang Wang, Yingxuan Zhang, Sina Zhai, Han Xia, Xilin Zhang
Summary: Pulmonary cryptococcosis is a serious fungal infection that is rare in immune-competent patients. It is often difficult to diagnose in time due to its clinical manifestations and radiological features similar to other pulmonary infections. However, metagenomic next-generation sequencing (mNGS) is a better diagnostic tool that can help clinicians distinguish pulmonary cryptococcosis from other atypical pulmonary infections.
FRONTIERS IN PUBLIC HEALTH
(2022)
Article
Immunology
John W. Baddley, Sharon C-A Chen, Carrie Huisingh, Kaitlin Benedict, Emilio E. DeBess, Eleni Galanis, Brendan R. Jackson, Laura MacDougall, Nicola Marsden-Haug, Hanna Oltean, John R. Perfect, Peter Phillips, Tania C. Sorrell, Peter G. Pappas
Summary: This study compared patients with cryptococcosis caused by Cryptococcus neoformans and Cryptococcus gattii, revealing differences in characteristics, clinical manifestations, and treatment outcomes between the two species.
CLINICAL INFECTIOUS DISEASES
(2021)
Review
Immunology
Yan Wang, Siddhi Pawar, Orchi Dutta, Keyi Wang, Amariliz Rivera, Chaoyang Xue
Summary: Macrophages play a crucial role in the defense against Cryptococcus infection by clearing pathogens and shaping the immune response. The interaction between Cryptococcus and macrophages determines the outcome of the infection and the susceptibility of hosts. Understanding the origin, polarization, activation, and effector functions of macrophages during Cryptococcus infection is important for developing immunotherapy for cryptococcosis treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Joseph Heitman
Summary: This Viewpoint is associated with the 25th anniversary of the American Society for Clinical Investigation's Stanley J. Korsmeyer Award, which recognizes scientific excellence, meritorious research, intellectual integrity, and mentoring of future researchers. The 2018 award honored Joseph Heitman for his contributions to understanding microbial pathogen evolution, disease causation, drug resistance, and discovery of immunosuppressive drug targets. Dr. Heitman has mentored numerous students, fellows, and researchers who have pursued successful careers in medicine and biomedical research.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Immunology
Zhengxia Wang, Wei Liu, Huidi Hu, Jingxian Jiang, Chen Yang, Xijie Zhang, Qi Yuan, Xiaofan Yang, Mao Huang, Yanming Bao, Ningfei Ji, Mingshun Zhang
Summary: This study found that decreased expression of CD146 in pulmonary tissues is associated with increased inflammatory response in pulmonary cryptococcosis. Furthermore, CD146 deficiency worsens the infection by C. neoformans.
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
(2023)
Article
Microbiology
Arjun Sukumaran, Brianna Ball, Jonathan R. Krieger, Jennifer Geddes-McAlister
Summary: The interactions between a host and microbe are crucial in determining the health and disease status of the host. Dual infections are common and contribute to disease severity in immunocompromised individuals. This study investigates the global reprogramming of host cells in response to immediate and established microbial infections with fungal and bacterial pathogens.
Review
Immunology
Herdson Renney de Sousa, Stefania de Frazao, Getulio Pereira de Oliveira Junior, Patricia Albuquerque, Andre Moraes Nicola
Summary: Cryptococcosis, caused by Cryptococcus spp, has a high mortality rate and lacks effective prevention and treatment methods. Understanding fungal virulence and host responses could lead to improved therapies. Studies using clinical isolates to correlate laboratory and patient data have provided valuable insights into the pathophysiology of cryptococcosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Enoch Tay, Sharon C-A Chen, Wendy Green, Ronald Lopez, Catriona L. Halliday
Summary: This study developed a new real-time PCR assay that can diagnose cryptococcosis rapidly and accurately, and differentiate between the two major causative agents. The assay showed high sensitivity and specificity, and can be applied to diverse clinical specimens.
Article
Microbiology
Zhixiao Sun, Ningfei Ji, Jingxian Jiang, Yuan Tao, Enrui Zhang, Xiaofan Yang, Zhengxia Wang, Zhongqi Chen, Mao Huang, Mingshun Zhang
Summary: Air pollution plays a crucial role in the increase of infectious lung diseases, particularly causing fatal fungal pneumonia in immunocompromised patients. The study shows that PM2.5 can upregulate CD146 expression in alveolar epithelial cells, promoting pulmonary infection of Cryptococcus neoformans, and CD146 deficiency may reduce the fungal burden of the infection.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Magdalena Florek, Urszula Nawrot, Agnieszka Korzeniowska-Kowal, Katarzyna Wlodarczyk, Anna Wzorek, Anna Wozniak-Biel, Magdalena Brzozowska, Jozef Galli, Anna Bogucka, Jaroslaw Krol
Summary: Fungi of Cryptococcus neoformans/C. gattii species complex are pathogens causing severe infections in humans and animals, with a mortality rate of up to 70% in humans. Understanding the population structure and distribution of these pathogens is crucial for studying the epidemiology of cryptococcosis. A study in Poland revealed a population of C. neoformans strains in animals, some of which exhibited resistance to antifungal treatment.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
M. Elizabeth Deerhake, Estefany Y. Reyes, Shengjie Xu-Vanpala, Mari L. Shinohara
Summary: Neutrophils play a critical role in acute pulmonary cryptococcosis by forming two distinct subsets during infection: Ox-PMN with oxidative stress signature and Cyt-PMN with enhanced cytokine gene expression. Ox-PMNs interact with the fungus to generate ROS, while Cyt-PMNs modulate cell-cell communication with dendritic cells and alveolar macrophages in response to Cn-derived ligands and cytokines. This suggests a division of labor in activated neutrophils during in vivo fungal infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Microbiology
Brittney N. Conn, Karen L. Wozniak
Summary: Cryptococcus neoformans is an opportunistic fungal pathogen that causes a significant number of deaths in HIV/AIDS patients each year. Innate phagocytes in the lungs, including dendritic cells and macrophages, are the first to encounter the pathogen and play a crucial role in its detection and clearance. However, C. neoformans has developed strategies to evade the host's immune system, and innate immune cells can also contribute to its pathogenesis. This review provides insights into the interactions between innate pulmonary phagocytes and C. neoformans based on recent literature.
Article
Microbiology
Caroline Patini Rezende, Patricia Kellen Martins Oliveira Brito, Thiago Aparecido Da Silva, Andre Moreira Pessoni, Leandra Naira Zambelli Ramalho, Fausto Almeida
Summary: The absence of Gal-3 does not significantly affect tissue histopathology, but may play a crucial role in modulating immune responses against cryptococcosis.
Article
Microbiology
Simone Becattini, Matthew T. Sorbara, Sohn G. Kim, Eric L. Littmann, Qiwen Dong, Gavin Walsh, Roberta Wright, Luigi Amoretti, Emily Fontana, Tobias M. Hohl, Eric G. Pamer
Summary: In response to acute immune activation, gut microbiota rapidly changes gene transcription and metabolite production, without affecting their relative abundance. Different immune stimuli can induce similar transcriptional profiles in commensal bacteria.
CELL HOST & MICROBE
(2021)
Article
Immunology
Allen W. Zhang, Sejal Morjaria, Anna Kaltsas, Tobias M. Hohl, Rekha Parameswaran, Dhruvkumar Patel, Wei Zhou, Jacqueline Predmore, Rocio Perez-Johnston, Justin Jee, Anthony F. Daniyan, Miguel-Angel Perales, Ying Taur
Summary: The use of G-CSF in cancer patients with COVID-19 may increase the risk of hospitalization, respiratory failure, and death. Careful consideration should be given to the potential risks and benefits of G-CSF treatment in neutropenic cancer patients with COVID-19.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Elizabeth Robilotti, Karissa Whiting, Anabella Lucca, Chester Poon, Rebecca Guest, Tracy McMillen, Krupa Jani, Alexander Solovyov, Suzanne Kelson, Kevin Browne, Scott Freeswick, Tobias M. Hohl, Deborah Korenstein, Denis Ruchnewitz, Michael Lassig, Marta Luksza, Benjamin Greenbaum, Venkatraman E. Seshan, N. Esther Babady, Mini Kamboj
Summary: A study of over 13000 healthcare personnel (HCP) showed that messenger RNA (mRNA) vaccine effectiveness (VE) against coronavirus disease 2019 (COVID-19) was 94% through initial 5 months of follow-up, with moderate VE reduction to 75% during subsequent Delta-dominant period. No hospitalizations occurred among vaccinated HCP throughout the study period.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Genetics & Heredity
Caoimhe E. O'Brien, Bing Zhai, Mihaela Ola, Sean A. Bergin, Eoin O. Cinneide, Isla O'Connor, Thierry Rolling, Edwin Miranda, N. Esther Babady, Tobias M. Hohl, Geraldine Butler
Summary: The Candida metapsilosis AC isolate, originating from a separate hybridization event, is different from the AB isolates, as it has not undergone introgression at the mating type-like locus and is in the early stages of genome stabilization.
G3-GENES GENOMES GENETICS
(2022)
Article
Medicine, Research & Experimental
Thierry Rolling, Bing Zhai, John Frame, Tobias M. Hohl, Ying Taur
Summary: Identification and analysis of fungal communities commonly rely on ITS-based amplicon sequencing. In this study, a customized DADA2-based pipeline was used to achieve high-resolution inference of fungal constituents. Quality filtering, sequencing bias, and database selection were identified as key variables determining the accuracy of sample inference. By fine-tuning the filtering process and introducing a wobble nucleotide, the representation of fungal communities was improved. Additionally, a BLAST-based algorithm showed higher reliability in species-level taxonomic annotation compared with the naive Bayesian classifier implemented in DADA2.
Article
Oncology
Roni Shouval, Nicholas R. Waters, Antonio L. C. Gomes, Corrado Zuanelli Brambilla, Teng Fei, Sean M. Devlin, Chi L. Nguyen, Kate A. Markey, Anqi Dai, John B. Slingerland, Annelie G. Clurman, Emily Fontana, Luigi A. Amoretti, Roberta J. Wright, Tobias M. Hohl, Ying Taur, Anthony D. Sung, Daniela Weber, Daigo Hashimoto, Takanori Teshima, Nelson J. Chao, Ernst Holler, Michael Scordo, Sergio A. Giralt, Miguel-Angel Perales, Jonathan U. Peled, Marcel R. M. van den Brink
Summary: We investigated the relationship between gut microbiota disruption and preparative conditioning regimens in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Our findings suggest that high-intensity conditioning regimens are associated with the most severe microbiota injury, while non-myeloablative regimens are associated with mild injury. Pretransplant microbial compositions are best preserved with certain conditioning regimens, while others result in loss of commensal bacteria and expansion of Enterococcus.
CLINICAL CANCER RESEARCH
(2023)
Article
Microbiology
Sean A. Bergin, Fang Zhao, Adam P. Ryan, Carolin A. Muller, Conrad A. Nieduszynski, Bing Zhai, Thierry Rolling, Tobias M. Hohl, Florent Morio, Jillian Scully, Kenneth H. Wolfe, Geraldine Butler
Summary: We analyzed the genomes of 170 C. parapsilosis isolates and identified multiple copy number variations (CNVs). We found that the increased copy number of the RTA3 gene is associated with resistance to the drug miltefosine. Additionally, we discovered that mutations in flippase genes can also contribute to resistance.
Article
Genetics & Heredity
Nicola T. Case, Judith Berman, David S. Blehert, Robert A. Cramer, Christina Cuomo, Cameron R. Currie, Iuliana Ene, Matthew C. Fisher, Lillian K. Fritz-Laylin, Aleeza C. Gerstein, N. Louise Glass, Neil A. R. Gow, Sarah J. Gurr, Chris Todd Hittinger, Tobias M. Hohl, Iliyan D. Iliev, Timothy Y. James, Hailing Jin, Bruce S. Klein, James W. Kronstad, Jeffrey M. Lorch, Victoria McGovern, Aaron P. Mitchell, Julia A. Segre, Rebecca S. Shapiro, Donald C. Sheppard, Anita Sil, Jason E. Stajich, Eva E. Stukenbrock, John W. Taylor, Dawn Thompson, Gerard D. Wright, Joseph Heitman, Leah E. Cowen
Summary: The fungal kingdom has diverse impacts on animal, plant, and ecosystem health, supporting life while also causing diseases. With increased climate change, antimicrobial resistance, and other global challenges, it is crucial to develop new approaches to combat fungal threats and harness their potential. This report provides recommendations and highlights major research advances and ideas discussed at a workshop to address these challenges.
G3-GENES GENOMES GENETICS
(2022)
Article
Immunology
Vanessa Espinosa, Orchi Dutta, Lena J. Heung, Keyi Wang, Yun-Juan Chang, Patricia Soteropoulos, Tobias M. Hohl, Mark C. Siracusa, Amariliz Rivera
Summary: This study reveals that neutrophils play a critical role in antifungal immunity by not only directly eliminating Aspergillus fumigatus conidia, but also by contributing to the activation of protective antifungal monocytes. This contribution is achieved, in part, through the regulation of STAT1-dependent functions.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Lena J. Heung, Darin L. Wiesner, Keyi Wang, Amariliz Rivera, Tobias M. Hohl
Summary: The respiratory tree plays a crucial role in maintaining sterilizing immunity against fungal pathogens. Fungal pneumonia usually occurs in individuals with compromised immune systems, such as HIV/AIDS patients, organ transplant recipients, and those undergoing corticosteroids treatment. Additionally, respiratory viruses and medical therapies used to treat viral infections can impair the lung's immune defense against fungi. Understanding lung-specific antifungal immunity has the potential to improve diagnostic, preventive, therapeutic, and vaccine strategies against fungal diseases of the lung.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Immunology
Mariano A. Aufiero, Neta Shlezinger, Mergim Gjonbalaj, Kathleen A. M. Mills, Andrea Ballabio, Tobias M. Hohl
Summary: Research has shown that myeloid phagocytes activate TFEB and TFE3 in response to Aspergillus fumigatus infection, which is crucial for lung immunity. However, genetic loss of TFEB and TFE3 does not significantly impact fungal control and host survival.
INFECTION AND IMMUNITY
(2023)
Article
Microbiology
Matthew R. James, Mariano A. Aufiero, Elisa M. Vesely, Sourabh Dhingra, Ko-Wei Liu, Tobias M. Hohl, Robert A. Cramer
Summary: This study identifies an important aspect of fungal biology in A. fumigatus that impacts susceptibility to leukocyte killing.
Article
Respiratory System
Guang-Shing Cheng, Kristina Crothers, Stefano Aliberti, Anne Bergeron, Michael Boeckh, Jason W. Chien, Catia Cilloniz, Keira Cohen, Nathan Dean, Charles S. Dela Cruz, Robert P. Dickson, Alexander L. Greninger, Chadi A. Hage, Tobias M. Hohl, Steven M. Holland, Barbara E. Jones, Joseph Keane, Mark Metersky, Rachel Miller, Anne Puel, Julio Ramirez, Marcos Restrepo, Ajay Sheshadri, Bashar Staitieh, Jeffrey Tarrand, Kevin L. Winthrop, Richard G. Wunderink, Scott E. Evans
Summary: Pneumonia poses a clinical burden on immunocompromised individuals, who are often excluded from clinical guidelines and trials. The lack of a widely accepted definition for immunocompromised host pneumonia hampers consistent care and research. To address this, the American Thoracic Society convened a workshop to define immunocompromised host pneumonia and its diagnostic criteria.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Review
Immunology
Michail S. S. Lionakis, Rebecca A. A. Drummond, Tobias M. M. Hohl
Summary: Pathogenic fungi have become major causes of infectious morbidity and mortality in patients with immunodeficiency conditions, and the spread of multidrug-resistant Candida auris has raised global public health concerns. Advances in understanding the cellular and molecular determinants of antifungal immunity provide potential strategies for risk stratification, prognosis, prophylaxis, and therapy against life-threatening fungal infections.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Deepika Awasthi, Sahil Chopra, Byuri A. Cho, Alexander Emmanuelli, Tito A. Sandoval, Sung-Min Hwang, Chang-Suk Chae, Camilla Salvagno, Chen Tan, Liliana Vasquez-Urbina, Jose J. Fernandez Rodriguez, Sara F. Santagostino, Takao Iwawaki, E. Alfonso Romero-Sandoval, Mariano Sanchez Crespo, Diana K. Morales, Iliyan D. Iliev, Tobias M. Hohl, Juan R. Cubillos-Ruiz
Summary: Infection with Candida albicans triggers hyperactivation of IRE1 alpha, leading to kidney immunopathology. Activation of MyD88 and dectin-1 by C. albicans causes ROS generation, ER stress, and overexpression of inflammatory mediators through IRE1 alpha. Inhibiting IRE1 alpha can mitigate inflammation and improve survival in systemic C. albicans infection.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
