Article
Biochemistry & Molecular Biology
Artur Muszynski, Kol A. Zarember, Christian Heiss, Joseph Shiloach, Lars J. Berg, John Audley, Arina Kozyr, David E. Greenberg, Steven M. Holland, Harry L. Malech, Parastoo Azadi, Russell W. Carlson, John Gallin
Summary: Granulibacter bethesdensis can infect patients with chronic granulomatous disease by its unique lipopolysaccharide structure characterized by strong acid resistance and low proinflammatory potency, potentially contributing to immune evasion and resistance to antimicrobial peptides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Nanoscience & Nanotechnology
Xiaodong Zhang, Xiaokai Chen, Yanli Zhao
Summary: Artificial nanosystems have the ability to modulate immune responses and can be used in vaccine development and treatment of bacterial infections and diseases. This review discusses the recent advances of nanosystems in vaccine development and immune activation, as well as the application of immune-suppressive nanosystems.
ACS APPLIED NANO MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Aotian Ouyang, Mengwei Zhang, Gailing Yuan, Xiaoling Liu, Jianguo Su
Summary: This study reveals that chitooligosaccharide (COS) has the ability to reverse cortisol-induced immunosuppression in fish and enhance the immune activity of macrophages. Oral administration of COS directly absorbed through the intestine significantly improves the innate immunity of blunt snout bream, leading to increased survival and reduced tissue damage. Thus, COS offers potential strategies for immunosuppression prevention and control in fish.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Immunology
Kei Amemiya, Jennifer L. Dankmeyer, Robert C. Bernhards, David P. Fetterer, David M. Waag, Patricia L. Worsham, David DeShazer
Summary: The research revealed that different Gram-negative pathogens activate host TLRs in different ways, with variations observed in activation patterns under different temperature conditions. Additionally, the study uncovered the role of the capsule of B. pseudomallei 1026b and the activation of TLR5 by purified flagellin or flagella attached to B. pseudomallei.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Immunology
Muhammad Nadeem Abbas, Saima Kausar, Bibi Asma, Wenhao Ran, Jingui Li, Zini Lin, Tiejun Li, Hongjuan Cui
Summary: The interaction between bacteria and insects has widespread implications due to their global distribution. It can directly impact human health as insects serve as disease vectors, and also have economic consequences. Moreover, it is linked to high mortality rates in economically important insects, resulting in significant economic losses.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ishita Tripathi-Giesgen, Christian Behrends, Arno F. Alpi
Summary: The ubiquitin system plays a crucial role in the host cellular defense program against bacterial infection, especially when certain bacteria are exposed to the host cytosol during invasion. Host cell E3 ubiquitin ligases contribute to the formation of a protective ubiquitin coat on invading pathogens, with their divergent ubiquitin conjugation mechanisms influencing the complexity of the anti-bacterial coating. Bacteria have evolved strategies to evade the activities of the host ubiquitin system.
Article
Immunology
Wei-Feng Wang, Xiao-Yong Xie, Kang Chen, Xiu-Li Chen, Wei-Lin Zhu, Huan-Ling Wang
Summary: The Chinese horseshoe crab relies on its innate immune system for pathogen defense, but the specific mechanisms underlying its abilities to distinguish and defend against invading microbes are still unclear. Through high-throughput sequencing and bioinformatics analysis, this study identified key signaling pathways activated in the Chinese horseshoe crab's hemolymph in response to Gram-negative bacteria, shedding light on the ancient original innate immune mechanism.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sara Olivera-Ardid, Daniel Bello-Gil, Magdiel Perez-Cruz, Cristina Costa, Mariana Camoez, M. Angeles Dominguez, Yara Ferrero-Alves, Jose Miguel Vaquero, Nailya Khasbiullina, Nadezhda V. Shilova, Nicolai V. Bovin, Rafael Manez
Summary: Eliminating natural anti-alpha Gal antibodies can provide protection against Gram-negative bacterial infections, enhance serum bactericidal activity, and improve bacteria opsonophagocytosis by macrophages.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Microbiology
Sophanit Mekasha, Dirk Linke
Summary: The article discusses the different types of secretion systems in Gram-negative bacterial fish pathogens and their potential roles in pathogenicity. It points out that the available information is fragmented and often descriptive, and hopes that the overview provided will help researchers systematically learn from the similarities and differences between the virulence factors and secretion systems of fish-pathogenic species described.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Travis B. Nielsen, Jun Yan, Brian M. Luna, Yuli Talyansky, Matthew Slarve, Robert A. Bonomo, Brad Spellberg
Summary: Research shows that antibacterial monoclonal antibody therapy enhances macrophage phagocytosis and rescues mice from lethal infections by utilizing complement, macrophages, and neutrophils. The level of bacterial burden does not directly correlate with survival. Furthermore, modulation of proinflammatory and anti-inflammatory cytokines is crucial for improving survival rates in antibody therapy against bacterial infections.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Kojiro Tsujihana, Kosuke Tanegashima, Yasuko Santo, Hiroyuki Yamada, Sota Akazawa, Ryuta Nakao, Keiko Tominaga, Risa Saito, Yasumasa Nishito, Ryu-Ichiro Hata, Tomonori Nakamura, Iori Murai, Yuka Kono, Maho Sugawa, Miki Tanioka, Gyohei Egawa, Masao Doi, Tadashi Isa, Kenji Kabashima, Takahiko Hara, Hitoshi Okamura
Summary: The epidermis, the outermost layer of skin, acts as a primary barrier against external pathogens. The early immune response in the epidermis is still not well understood, but research has shown that keratinocytes exhibit circadian fluctuations and can activate innate immunity. In nocturnal mice, the expression of CXCL14, a chemokine, is associated with clearance of the skin pathogen Staphylococcus aureus, with high expression during the subjective daytime and low expression at night. However, in diurnal primates like marmosets, CXCL14 expression is reversed. These findings suggest that the circadian production of CXCL14 plays a role in suppressing skin bacterial proliferation by activating the innate immune system.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Infectious Diseases
Patrizia Ferraboschi, Samuele Ciceri, Paride Grisenti
Summary: Lysozyme is a 14 kDa protein found in mucosal secretions and tissues of animals and plants, playing a key role in innate immunity by protecting against bacteria, viruses, and fungi. It is known to have antimicrobial properties and has been studied for various applications as an alternative antibiotic in medicine, veterinary, and food preservation industries. The synergistic effects of lysozyme with other antimicrobial compounds are also highlighted in this review.
Article
Immunology
Zihao Deng, Yanyang Yang, Jiazhen Luo, Biling Zhang, Jiyong Liu, Guanghou Shui, Renjie Jiao, Chuanxian Wei
Summary: This study assessed the temporal changes of lipid metabolism profiles during infection using integrated transcriptomics and lipidomics analysis. It identified the importance of ergosterol in host defense against pathogens, with its level increased upon bacterial infection. The study also showed that increasing ergosterol level promotes host survival against bacterial challenges.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Richa Mishra, Pandikannan Krishnamoorthy, Himanshu Kumar
Summary: Host innate immunity plays a crucial role in combating microbial infections, but some pathogenic bacteria have strategies to evade the immune system. MicroRNAs are believed to modulate host immune responses during bacterial infections, with miR-30e-5p identified as a potential candidate for HDT.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Genetics & Heredity
Alexia L. Carboni, Mark A. Hanson, Scott A. Lindsay, Steven A. Wasserman, Bruno Lemaitre
Summary: Cecropins are small helical secreted peptides with antimicrobial activity that play an important role in host defense. Experimental studies have shown that Cecropins play a role in defense against Gram-negative bacteria and fungi in fruit flies.
Article
Allergy
SuJin Hwang, Christina Tatsi, Hye Sun Kuehn, Julie E. Niemela, Jennifer Stoddard, Yan Su, Maya Lodish, Gulbu Uzel, Rosanne Spolski, Warren J. Leonard, Steven M. Holland, Thomas A. Fleisher, Constantine A. Stratakis, Sergio D. Rosenzweig
Summary: This study investigated the immunological effects of pediatric endogenous Cushing syndrome (eCs) and its treatment. The results showed that the decrease in thymic output, lymphocyte proliferation, and increase in apoptosis were the underlying causes of T-cell lymphopenia in eCs patients. Additionally, IL-21 levels were decreased in both natural and in vitro glucocorticoid environments, but the addition of IL-21 in vitro counteracted the proapoptotic effects of glucocorticoid therapy.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Cell Biology
Weixin Wang, Rui Chen, Stephenie Droll, Emily Barber, Layla Saleh, Meghan Corrigan-Cummins, Megan Trick, Vollter Anastas, Nga Voong Hawk, Zhen Zhao, Donald C. Vinh, Amy Hsu, Dennis D. Hickstein, Steven M. Holland, Katherine R. Calvo
Summary: GATA2 deficiency leads to cytopenias and susceptibility to infections. Increased expression of miR-181c and decreased levels of MCL1 were found in GATA2 deficiency cells, possibly contributing to elevated cell death and cytopenia. GATA2 represses miR-181c expression, while knockdown of GATA2 results in increased miR-181c expression.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Hematology
Robert R. West, Katherine R. Calvo, Lisa J. Embree, Weixin Wang, Laura M. Tuschong, Thomas R. Bauer, Desiree Tillo, Justin Lack, Stephenie Droll, Amy P. Hsu, Steven M. Holland, Dennis D. Hickstein
Summary: Patients with GATA2 deficiency have germline mutations in the GATA2 transcription factor gene, which predispose them to myeloid malignancies. Somatic mutations in ASXL1 and STAG2 are associated with lower survival probability, while mutations in DNMT3A are found in early stages of the disease. Chromatin-related genes and cohesin genes characterize the progression of GATA2 deficiency.
Article
Hematology
Diana X. Nichols-Vinueza, Mark Parta, Nirali N. Shah, Jennifer M. Cuella-Rodriguez, Thomas R. Bauer, Robert R. West, Amy P. Hsu, Katherine R. Calvo, Seth M. Steinberg, Luigi D. Notarangelo, Steven M. Holland, Dennis D. Hickstein
Summary: In patients with GATA2 deficiency, a busulfan-based HSCT regimen can reverse the hematologic disease phenotype, and the use of post-transplant cyclophosphamide (PT/Cy) reduces the risk of both acute and chronic GVHD.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Immunology
Mark Parta, Jennifer Cuellar-Rodriguez, Juan Gea-Banacloche, Jing Qin, Corin Kelly, Christa S. Zerbe, Steven M. Holland, Harry L. Malech, Elizabeth M. Kang
Summary: We analyzed events and therapies related to febrile neutropenia in patients receiving hematopoietic cell transplantation (HCT) for chronic granulomatous disease (CGD). The study found that fever prior to neutropenia was common and some patients experienced Gram-negative bacterial infection before or during neutropenia. Empiric therapy with noncarbapenem antibiotics was commonly used, but carbapenems were also given in some cases. No deaths related to infection associated with neutropenia occurred.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Article
Multidisciplinary Sciences
Jeremy Manry, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jeremie Rosain, Quentin Philippot, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina Garcia-Prat, Lucy Bizien, Alba Parra-Martinez, Rui Yang, Liis Haljasmagi, Melanie Migaud, Karita Sarekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles-Edouard Luyt, Blanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesus Troya, Sophie Trouillet-Assant, Alexandre Belot, Kahina Saker, Pierre Garcon, Jacques G. Riviere, Jean-Christophe Lagier, Stephanie Gentile, Lindsey B. Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre-Louis Tharaux, Damien Sene, Alain Stepanian, Bruno Megarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, Jose Luis Franco, Juan-Manuel Anaya, Jordi Sole-Violan, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia M. Delmonte, Yu Zhang, Andrew L. Snow, Steven M. Holland, Catherine M. Biggs, Marcela Moncada-Velez, Andres Augusto Arias, Lazaro Lorenzo, Soraya Boucherit, Dany Anglicheau, Anna M. Planas, Filomeen Haerynck, Sotirija Duvlis, Tayfun Ozcelik, Sevgi Keles, Ahmed A. Bousfiha, Jalila El Bakkouri, Carolina Ramirez-Santana, Stephane Paul, Qiang Pan-Hammarstrom, Lennart Hammarstrom, Annabelle Dupont, Alina Kurolap, Christine N. Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila A. Barreiros, Elena Dominguez-Garrido, Mateus Vidigal, Mayana Zatz, Diederik van de Beek, Sabina Sahanic, Ivan Tancevski, Yurii Stepanovskyy, Oksana Boyarchuk, Yoko Nukui, Miyuki Tsumura, Loreto Vidaur, Stuart G. Tangye, Sonia Burrel, Darragh Duffy, Lluis Quintana-Murci, Adam Klocperk, Nelli Y. Kann, Anna Shcherbina, Yu-Lung Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Felipe Reyes, Angelique Chauvineau-Grenier, Fabienne Venet, Guillaume Monneret, Michel C. Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris-Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam H. Dyer, Sean Kennelly, Nollaig M. Bourkeh, Rabih Halwan, Fatemeh Saheb Sharif-Askar, Karim Dorgham, Jerome Sallette, Souad Mehlal Sedkaoui, Suzan AlKhater, Raul Rigo-Bonnin, Francisco Morandeira, Lucie Roussel, Donald C. Vinh, Christian Erikstrup, Antonio Condino-Neto, Carolina Prando, Anastasiia Bondarenko, Andras N. Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilguvar, Richard P. Lifton, Shrikant Mane, Mark S. Anderson, Bertrand Boisson, Vivien Beziat, Shen-Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Part Peterson, Trine H. Mogensen, Lee Rowen, James Mond, Stephanie Debette, Xavier de Lamballerie, Charles Burdet, Lila Bouadma, Marie Zins, Pere Soler-Palacin, Roger Colobran, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martinez-Picado, Didier Raoult, Marc Vasse, Peter K. Gregersen, Lorenzo Piemonti, Carlos Rodriguez-Gallego, Luigi D Notarangelo, Helen C. Su, Kai Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles M. Rice, Pierre Tiberghien, Qian Zhang, Jean-Laurent Casanova, Laurent Abel, Aurelie Cobat
Summary: This study investigates the impact of autoimmunity on COVID-19-related deaths and finds that individuals carrying autoantibodies neutralizing type I interferons are at higher risk of death, with the risk decreasing with age.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Linchen He, Chan Wang, Jiyuan Hu, Zhan Gao, Emilia Falcone, Steven M. Holland, Martin J. Blaser, Huilin Li
Summary: Dynamic changes of microbiome communities play important roles in human health and diseases. A novel statistical method called ARZIMM is proposed to model the temporal dynamic patterns of microbiome and quantify the microbial interactions and community stability simultaneously.
FRONTIERS IN GENETICS
(2022)
Article
Hematology
Katelyn J. McCann, Stephen M. Christensen, Devon H. Colby, Peter J. McGuire, Ian A. Myles, Christa S. Zerbe, Clifton L. Dalgard, Gauthaman Sukumar, Warren J. Leonard, Beth A. McCormick, Steven M. Holland
Summary: This study identifies an IFNy-induced, NAMPT-dependent, NAD+ salvage pathway that is critical for the activation of human monocytes. IFNy reprograms monocyte metabolism by increasing oxygen consumption rates through the oxidative phenotype driven by the IFNy-induced reprogramming of NAD+ metabolism.
Article
Microbiology
Jigar Desai, Amanda Urban, Doris Z. Swaim, Benjamin Colton, Lilian W. Kibathi, Elise M. N. Ferre, Pamela Stratton, Melissa A. Merideth, Sally Hunsberger, Theresa Matkovits, Raphael Mannino, Steven M. Holland, Edmund Tramont, Michail S. Lionakis, Alexandra F. Freeman
Summary: A new oral formulation of Amphotericin B (CAMB) was evaluated for its efficacy in mouse models and patients with azole-resistant chronic mucocutaneous candidiasis (CMC). CAMB significantly reduced tongue and vaginal fungal burdens in mice and showed good efficacy and tolerability in CMC patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Hematology
Ryan L. Wong, Sarah Sackey, Devin Brown, Shantha Senadheera, Katelyn Masiuk, Jason P. Quintos, Nicole Colindres, Luke Riggan, Richard A. Morgan, Harry L. Malech, Roger P. Hollis, Donald B. Kohn
Summary: X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene, leading to impaired infection elimination by phagocytic cells. A bioinformatics-guided approach was used to identify enhancer elements of the CYBB gene and develop MyeloVec, a physiologically regulated lentiviral vector (LV) for the treatment of X-CGD. MyeloVec showed improved expression, efficient gene transfer to hematopoietic stem and progenitor cells (HSPCs), and successful correction of X-CGD in a mouse model, making it a promising clinical treatment for X-CGD.
Review
Immunology
Scott D. Kobayashi, Frank R. DeLeo, Mark T. Quinn
Summary: Neutrophils are an important component of innate host defense, with a high production rate and rapid mobilization to infected tissues. They contain abundant antimicrobial molecules, but their turnover and activation are tightly regulated. Microbial pathogens can affect the apoptosis and cytolysis of neutrophils, altering their function.
IMMUNOLOGICAL REVIEWS
(2023)
Editorial Material
Clinical Neurology
Shaia Bierman-Chow, Steven M. Holland, Amy P. Hsu, Cindy Palmer, John Lynch, Yair Mina, HyunJoo (Sophie) Cho
Summary: This study characterized the clinical, laboratory, and imaging findings of 10 patients with GATA2 deficiency who presented with early-onset ischemic stroke. The results suggest a link between GATA2 deficiency and stroke, emphasizing the need for further research to understand this unique vulnerability within this patient population.
Article
Biochemistry & Molecular Biology
Hannah Mason, Ganesha Rai, Arina Kozyr, Nathaniel De Jonge, Emily Gliniewicz, Lars J. Berg, Gal Wald, Cayce Dorrier, Mark J. Henderson, Alexey Zakharov, Tristan Dyson, John Audley, Anthony M. Pettinato, Elias Carvalho Padilha, Pranav Shah, Xin Xu, Thomas L. Leto, Anton Simeonov, Kol A. Zarember, Dorian B. McGavern, John I. Gallin
Summary: NADPH oxidases (NOX's) and the reactive oxygen species (ROS) they produce are involved in various physiological processes, but excessive ROS production is associated with several diseases. In this study, a small molecule inhibitor, NCATS-SM7270, was developed and shown to specifically inhibit NOX2 activity in human and mouse granulocytes. The role of different NOX isoforms in mild traumatic brain injury (mTBI) was investigated, and it was found that NOX2 deficiency provided protection against mTBI pathology, while NOX4 deficiency exacerbated the injury. Treatment of mice with NCATS-SM7270 after mTBI reduced cortical cell death in a dose-dependent manner, and also partially reversed cortical damage in NOX4-deficient mice. These findings highlight the potential of NCATS-SM7270 as a specific inhibitor of NOX2 in protecting against NOX2-dependent cell death in mTBI.
Review
Genetics & Heredity
Marie Morimoto, Elena-Raluca Nicoli, Chulaluck Kuptanon, Joseph C. Roney, Jenny Serra-Vinardell, Prashant Sharma, David R. Adams, John Gallin, Steven M. Holland, Sergio D. Rosenzweig, Jose Barbot, Carla Ciccone, Marjan Huizing, Camilo Toro, William A. Gahl, Wendy J. Introne, May Christine Malicdan
Summary: The study identified 11 novel pathogenic LYST variants in patients with CHS, adding to a total of 147 variants in LYST. A genotype-phenotype correlation was observed, indicating that individuals with missense or in-frame variants usually have milder disease compared to those with nonsense or frameshift variants.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Microbiology
Frank R. DeLeo, Adeline R. Porter, Scott D. Kobayashi, Brett Freedman, Mingju Hao, Jianping Jiang, Yi-Tsung Lin, Barry N. Kreiswirth, Liang Chen, Joanna B. Goldberg
Summary: Klebsiella pneumoniae is a significant cause of healthcare-associated infections worldwide, with different strains causing infections in individuals with comorbidities and healthy individuals. The emergence of strains with both multidrug resistance and hypervirulence complicates the understanding of the immune response against this pathogen.