Article
Immunology
Allison M. Owen, Liming Luan, Katherine R. R. Burelbach, Margaret A. A. McBride, Cody L. L. Stothers, Olivia A. A. Boykin, Kalkena Sivanesam, Jessica F. F. Schaedel, Tazeen K. K. Patil, Jingbin Wang, Antonio Hernandez, Naeem K. K. Patil, Edward R. R. Sherwood, Julia K. K. Bohannon
Summary: Immunocompromised populations are at high risk of life-threatening infections, and strategies to protect these patients are urgently needed. This study explores the use of trained immunity, which enhances the immune response to subsequent infections, as a promising approach. The researchers demonstrate that the MyD88-dependent signaling pathway plays a critical role in TLR-mediated trained immunity, providing valuable insights into the mechanisms underlying this process.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Pablo Mata-Martinez, Marta Bergon-Gutierrez, Carlos del Fresno
Summary: Dectin-1, a C-type lectin receptor, plays a crucial role in antifungal responses and immune memory. It recognizes various ligands and triggers different immune reactions. However, the underlying mechanisms of its involvement in trained immunity are not fully understood.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Hematology
Helin Tercan, Niels P. Riksen, Leo A. B. Joosten, Mihai G. Netea, Siroon Bekkering
Summary: Trained immunity is a persistent hyperresponsive phenotype developed by innate immune cells after stimulation, causing cells to remember pathogens and endogenous molecules. While providing cross-protection in infectious diseases, trained immunity may lead to excessive immune responses in diseases driven by chronic systemic inflammation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Immunology
Ella A. Zuiderwijk-Sick, Celine van der Putten, Raissa Timmerman, Jennifer Veth, Erica M. Pasini, Linda van Straalen, Paul van der Valk, Sandra Amor, Jeffrey J. Bajramovic
Summary: Exposure to IL-4 induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Additionally, IL-4 exposure broadly impairs TLR-induced cytokine production and inhibits microglial innate immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Samanta C. Funes, Mariana Rios, Ayleen Fernandez-Fierro, Maria S. Di Genaro, Alexis M. Kalergis
Summary: A dysregulated immune response is a characteristic of autoimmune and autoinflammatory disorders. Monocytes and macrophages (Mo/Ma) have been found to significantly contribute to the development of both types of diseases, but their functional plasticity makes it difficult to understand their exact role.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Vaclav Vetvicka, Petr Sima, Luca Vannucci
Summary: Trained immunity, achieved through epigenetic reprogramming, is less specific and may provide cross-protection. However, observed changes could also be influenced by immune modulators, and the question of trained immunity in cells with a short lifespan remains unresolved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Hematology
Robin P. Choudhury, Laurienne Edgar, Mikael Ryden, Edward A. Fisher
Summary: Physiological functions are intricately intertwined, with evidence from immunometabolism field showing that cells can be programmed by changes in metabolic environment through epigenetic modifications, causing persistent changes. Understanding these processes can have significant implications for the diagnosis and treatment of diabetes and related metabolic states.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Guotao Peng, Sandeep Keshavan, Lucia Delogu, Yuyoung Shin, Cinzia Casiraghi, Bengt Fadeel
Summary: This study demonstrates that two-dimensional transition metal dichalcogenides (TMDs), specifically MoS2, can trigger trained immunity in human macrophages. This induction of trained immunity involves epigenetic pathway and metabolic rewiring, leading to changes in immune gene expression and cellular metabolism.
Article
Medicine, Research & Experimental
Yuchen Pan, Jingman Li, Xiaoyu Xia, Jiali Wang, Qi Jiang, Jingjing Yang, Huan Dou, Huaping Liang, Kuanyu Li, Yayi Hou
Summary: In this study, BSNPs nanoparticles were successfully synthesized and shown to effectively reprogram macrophages to enhance trained immunity. BSNPs protected mice against sepsis and secondary infections caused by Escherichia coli. The study also revealed the signaling and regulatory mechanisms of BSNP-induced trained immunity, which were found to be mTOR-dependent.
Review
Hematology
Charles Drummer, Fatma Saaoud, Ying Shao, Yu Sun, Keman Xu, Yifan Lu, Dong Ni, Diana Atar, Xiaohua Jiang, Hong Wang, Xiaofeng Yang
Summary: Innate immune cells can develop trained immunity after exposure to stimuli like lipopolysaccharides and oxLDL, leading to altered responses upon subsequent challenges. This phenomenon is important for host defense and inflammation, particularly in cardiovascular and metabolic diseases. Trained immunity involves rewiring cellular metabolism and epigenetic remodeling that enhance gene transcription and proinflammatory immune responses, contributing to chronic inflammation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Microbiology
Athanasios Ziogas, Mariolina Bruno, Roy van der Meel, Willem J. M. Mulder, Mihai G. Netea
Summary: Trained immunity is a memory for innate immune responses, enhancing resistance against pathogens. Dysregulated trained immunity can lead to diseases, therefore studying the mechanisms of trained immunity is important for disease prevention and treatment.
CELL HOST & MICROBE
(2023)
Article
Biochemistry & Molecular Biology
Tze-Yen Lin, Danye Jiang, Wan-Ru Chen, Jhih Syuan Lin, Xin-Yu Zhang, Chih-Hung Chen, Chia-Lang Hsu, Liang-Chuan Lai, Ping-Hung Chen, Kai-Chien Yang, Lauren H. Sansing, Che-Feng Chang
Summary: A high-salt diet leads to sustained sterile inflammation and worsens tissue injury, impairing long-term brain recovery after intracerebral hemorrhage. The mechanism involves the downregulation of NR4a family and mitochondrial oxidative phosphorylation, leading to innate immune priming and training in hematopoietic stem and progenitor cells. This research uncovers the link between high-salt diet-induced innate immune memory and persistent dysregulated inflammatory responses, highlighting NR4a1 as a potential therapeutic target.
Article
Cell Biology
Anaisa V. Ferreira, Valerie A. C. M. Koeken, Vasiliki Matzaraki, Sarantos Kostidis, Juan Carlos Alarcon-Barrera, L. Charlotte J. de Bree, Simone J. C. F. M. Moorlag, Vera P. Mourits, Boris Novakovic, Martin A. Giera, Mihai G. Netea, Jorge Dominguez-Andres
Summary: The innate immune system displays heterologous memory characteristics, with stronger responses to a secondary challenge, known as trained immunity. Glutathione metabolism plays a role in the induction of trained immunity and may have implications for human diseases.
Article
Immunology
Huanhuan Ning, Jian Kang, Yanzhi Lu, Xuan Liang, Jie Zhou, Rui Ren, Shan Zhou, Yong Zhao, Yanling Xie, Lu Bai, Linna Zhang, Yali Kang, Xiaojing Gao, Mingze Xu, Yanling Ma, Fanglin Zhang, Yinlan Bai
Summary: In this study, researchers constructed a recombinant BCG vaccine (rBCG-DisA) with di-adenylate cyclase (DisA) and found that it induced enhanced immune responses in mice, leading to trained immunity and adaptive immunity. Additionally, rBCG-DisA showed promising potential in protecting against M. tuberculosis infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Katherine A. Robinson, Naveed Akbar, Kajus Baidzajevas, Robin P. Choudhury
Summary: Metabolic diseases are associated with inflammation, which negatively affects cardiovascular health. Evidence shows that long-term hyperactivation of innate immune cells and their bone marrow progenitors, known as trained immunity, accelerates atherosclerosis in cardiometabolic diseases. Understanding the mechanisms of trained immunity can lead to the development of novel therapies for reducing cardiovascular risk in metabolic diseases.
Article
Public, Environmental & Occupational Health
David Chaima, Harry Pickering, John D. Hart, Sarah E. Burr, Joanna Houghton, Kenneth Maleta, Khumbo Kalua, Robin L. Bailey, Martin J. Holland
Summary: The study found that mass azithromycin treatment did not significantly impact gut microbiota diversity in children aged 1 to 59 months in rural Malawi. However, four biannual rounds of treatment were associated with increased abundance of Prevotella.
FRONTIERS IN PUBLIC HEALTH
(2022)
Article
Immunology
Gathoni Kamuyu, Giuseppe Ercoli, Elisa Ramos-Sevillano, Sam Willcocks, Chidchamai Kewcharoenwong, Pattarachai Kiratisin, Peter W. Taylor, Brendan W. Wren, Ganjana Lertmemongkolchai, Richard A. Stabler, Jeremy S. Brown
Summary: The complement system plays an important role in the defense against bacterial infections, but different strains of A. baumannii show variations in their sensitivity to the complement system. These differences are partially independent of capsule composition or size, and variations in serum resistance among strains are not solely determined by MAC formation on bacterial surfaces.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Amber Barton, Athumani Ramadhani, Elias Mafuru, Tara Mtuy, Patrick Massae, Aiweda Malissa, Tamsyn Derrick, Joanna Houghton, Anna Harte, Thomas Payne, Harry Pickering, Matthew J. Burton, Chrissy H. Roberts, Martin J. Holland
Summary: HLA typing was performed on 336 Maasai participants using locus-specific amplicon sequencing at the HLA-A,-B,-C,-DRB1,-DQB1 and-DPB1 loci. The participants were recruited from three villages in North Tanzania for a study on risk factors for trachomatous scarring in children. Apart from the HLA-A locus, all other loci significantly deviated from Hardy-Weinberg equilibrium, possibly due to high relatedness among individuals: 238 individuals shared a household with at least one other participant. The most frequent alleles at each locus were A*68:02 (14.3%), B*53:01 (8.4%), C*06:02 (19.2%), DRB1*13:02 (17.7%), DQB1*02:01 (16.9%), and DPB1*01:01 (15.7%), while the most common inferred haplotype was A*68:02 B*18:01 C*07:04 DRB1*08:04 DQB1*04:02 DPB1*04:01 (1.3%).
Editorial Material
Immunology
Amber Barton, Harry Pickering, Thomas Payne, Nkoyo Faal, Ansumana Sillah, Anna Harte, Robin L. Bailey, David C. W. Mabey, Chrissy H. Roberts, Martin J. Holland
Summary: HLA DRB1, DQB1, and DPB1 alleles were determined for 939 Gambian individuals using locus-specific amplicon sequencing. The participants were from various regions of The Gambia and divided into two studies: a family study investigating the relationship between host genotype and trachomatous scarring (N = 796) and a cohort study identifying correlates of trachoma immunity (N = 143). Deviation from Hardy-Weinberg equilibrium was observed in all loci, likely due to the inclusion of family members in the study population. The most common alleles for HLA-DRB1, DQB1, and DPB1 were DRB1*13:04 (18.8%), DQB1*03:19 (27.9%), and DPB1*01:01 (25.4%), respectively. The participants belonged to different ethnic groups, including Mandinka, Fula, Wolof, and Jola.
Article
Cell Biology
Giorgio Ottaviano, Christos Georgiadis, Soragia Athina Gkazi, Farhatullah Syed, Hong Zhan, Annie Etuk, Roland Preece, Jan Chu, Agnieszka Kubat, Stuart Adams, Paul Veys, Ajay Vora, Kanchan Rao, Waseem Qasim
Summary: This study demonstrates the feasibility, safety, and therapeutic potential of CRISPR-engineered immunotherapy. By using genome editing techniques, allogeneic T cells were modified to provide off-the-shelf alternatives to autologous CAR T cell therapies, showing promising results in the treatment of B-ALL.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Correction
Immunology
Anja Weinreich Olsen, Ida Rosenkrands, Martin J. Holland, Peter Andersen, Frank Follmann
Article
Public, Environmental & Occupational Health
Harry Pickering, Athumani M. M. Ramadhani, Patrick Massae, Elias Mafuru, Aiweda Malisa, Kelvin Mbuya, William Makupa, Tara Mtuy, Tamsyn Derrick, Joanna Houghton, Robin L. L. Bailey, David C. W. Mabey, Matthew J. J. Burton, Martin J. J. Holland
Summary: This study investigated the changes in the ocular microbiome in children with trachoma. The results showed that mass drug administration with azithromycin effectively cleared C. trachomatis infection and reduced other non-chlamydial ocular pathogens, promoting restoration of a normal ocular microbiome.
FRONTIERS IN PUBLIC HEALTH
(2022)
Editorial Material
Immunology
Hiroshi Eguchi, Jerome Ozkan, Martin J. Holland
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Hematology
Ilaria M. Michelozzi, Eduardo Gomez-Castaneda, Ruben V. C. Pohle, Ferran Cardoso Rodriguez, Jahangir Sufi, Pau Puigdevall Costa, Meera Subramaniyam, Efstratios Kirtsios, Ayad Eddaoudi, Si Wei Wu, Aleks Guvenel, Jonathan Fisher, Sara Ghorashian, Martin A. Pule, Christopher J. Tape, Sergi Castellano, Persis J. Amrolia, Alice Giustacchini
Summary: We have described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that exhibits enhanced activation and cytokine polyfunctionality compared with high-affinity FMC63 CAR. This enhanced functionality is a result of antigen-dependent priming induced by residual CD19-expressing B cells. CAT CAR shows excellent toxicity profile, enhanced in vivo expansion, and long-term persistence in a phase 1 clinical study.
Article
Immunology
Amber Barton, Ida Rosenkrands, Harry Pickering, Nkoyo Faal, Anna Harte, Hassan Joof, Pateh Makalo, Manon Ragonnet, Anja Weinreich Olsen, Robin L. L. Bailey, David C. W. Mabey, Frank Follmann, Jes Dietrich, Martin J. J. Holland
Summary: Serum samples from children in five trachoma endemic villages in the Gambia were analyzed to investigate the association between systemic antibody features and susceptibility to Chlamydia trachomatis infection. The study found that systemic infection-induced IgG and functional antibody responses do not appear to protect against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Infectious Diseases
Robert Butcher, Sheikh Jarju, Dolapo Obayemi, Adedapo Olufemi Bashorun, Hristina Vasileva, Hannah Bransbury-Hare, Orighomisan Agboghoroma, Lamin Drammeh, Martin Holland, Emma Harding-Esch, Ed Clarke
Summary: This study aimed to determine the prevalence of five treatable sexually transmitted infections (STIs) in Gambian women. The results showed that 9.8% of women tested positive for at least one STI, with trichomoniasis being the most common. Monitoring systems should be established.
BMC INFECTIOUS DISEASES
(2023)
Review
Virology
Ehsan Ghasemian, Emma Harding-Esch, David Mabey, Martin J. Holland
Summary: The global incidence of sexually transmitted infections (STIs) remains high, with co-infections of multiple pathogens being prevalent. Chlamydia trachomatis (CT) is the most reported bacterial STI worldwide, co-infecting with viral and other bacterial STIs. This review provides an overview of the epidemiology of these co-infections and specifically focuses on the underlying mechanisms by which CT influences the transmission and infection dynamics of HIV and HSV. It also explores the complex relationship between CT and HPV infection.
Article
Infectious Diseases
Amber Barton, Nkoyo Faal, Athumani Ramadhani, Tamsyn Derrick, Elias Mafuru, Tara Mtuy, Patrick Massae, Aiweda Malissa, Hassan Joof, Pateh Makalo, Ansumana Sillah, Anna Harte, Harry Pickering, Robin Bailey, David C. W. Mabey, Matthew J. Burton, Martin J. Holland
Summary: In this study, tear samples from individuals with trachoma were analyzed to investigate the cytokines and antimicrobial proteins associated with the disease. The results showed that inflammatory chemokines and lysozyme were increased in scarring, while IL-8 was increased during infection. Longitudinal profiling of these proteins in a separate cohort study revealed an increase in the levels of inflammatory chemokines before and after detectable infection, particularly in cases of repeated infections.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Hematology
Ilaria M. Michelozzi, Eduardo Gomez-Castaneda, Ruben V. C. Pohle, Ferran Cardoso Rodriguez, Jahangir Sufi, Pau Puigdevall Costa, Meera Subramaniyam, Efstratios Kirtsios, Ayad Eddaoudi, Si Wei Wu, Aleks Guvenel, Jonathan Fisher, Sara Ghorashian, Martin A. Pule, Christopher J. Tape, Sergi Castellano, Persis J. Amroia, Alice Giustacchini
Summary: A low-affinity second-generation CD19 CAR showed improved expansion, cytotoxicity, and antitumor efficacy compared to a high-affinity CAR in preclinical models. In a phase 1 clinical study, the low-affinity CAR demonstrated an excellent toxicity profile and long-term persistence. In vitro characterization revealed that low-affinity CAR T cells had enhanced activation and a distinct transcriptomic and protein profile, with increased activation and cytokine polyfunctionality compared to high-affinity CAR T cells.
Meeting Abstract
Respiratory System
T. Masonou, M. Woodall, E. Robinson, A. Eddaoudi, K. M. Case, J. O. Canseco, P. Solanki, L. Elton, L. B. Arruda, T. D. Mchugh, R. Hynds, C. Butler, M. Nikolic, R. L. Smyth, C. M. Smith
EUROPEAN RESPIRATORY JOURNAL
(2022)