tbuckley/cabot-search huggingface dataset:
The Expression of TIM3 on Marrow-Infiltrating T Cells Is Increased in Patients with Blood Cancers Who Relapse Early after Hematopoietic Stem Cell Transplantation
Authors: Thi Thuy Duong Pham, Su-Young Choi, Buyeon Heo, Sang-Woo Lee, Myung-Won Lee, Jung-Hyun Park, Yunseon Jang, Deog-Yeon Jo, Jaeyul Kwon, Ik Chan Song, Jeong Suk Koh
Journal: Blood (2024)
First-in-Human Phase 1a Clinical Trial of the Investigational New Drug ST-001, a Novel Nano-Phospholipid Dispersion Formulation of Fenretinide, in Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma
Authors: Ali Moiin, Yamini Donekal, Louis Scarmoutzos, Michael Burns, Robert Patterson, Earle Holsapple, Ajay K. Gopal, Ralph Parchment, Oleg Akilov
Journal: Blood (2024)
Role of Factor VIII As a Regulator of Angiogenesis and Promoter of Endothelial Barrier Stability
Authors: Cristina Olgasi, Alessia Cucci, Simone Assanelli, Chiara Sgromo, Chiara Borsotti, Giorgia Venturin, Stefan Winge, Roberto Santi, Antonia Follenzi
Journal: Blood (2024)
A Phase II Clinical Study Exploring the Safety and Efficacy of the Oral PI3Kδ Inhibitor, Linperlisib, in Relapsed Refractory T Cell Lymphoma
Authors: Swaminathan P Iyer, Ranjit Nair, Neha Mehta-Shah, Don A. Stevens, Alessandra Tucci, Antonio Pinto, Pier Luigi Zinzani
Journal: Blood (2024)
Characterization of Hemophagocytic Lymphohistiocytosis Associated with Myeloid Neoplasms at Single-Cell Resolution
Authors: Ke Shang, Guangshuai Teng, Yuhui Zhang, Yifan Duan, Chenxiao Du, Yan Wang, Huiqin Zhang, Xuelian Cheng, Yuan Zhou, Yajing Chu, Weiping Yuan, Jie Bai
Journal: Blood (2024)
Utilizing Large Language Models to Automate Prognostication in Patients with Myelofibrosis: A Retrospective Cohort Study
Authors: Muhammad Ali Khan, Umair Ayub, Muhammad Umair Anjum, Salman Ayub Jajja, Syed Arsalan Naqvi, Zaryab Bin Riaz, Ammad Raina, Irbaz Bin Riaz, Jeanne Palmer
Journal: Blood (2024)
Protein Energy Malnutrition and in-Hospital Outcomes Among Hospitalized Patients with Immune Thrombocytopenia: A United States Collaborative Network Cohort Study
Authors: Colton Frisco Jones, Elvis Obomanu, Tarfa Verinumbe, Hilary A Elom, Hasiya Yusuf, Karecia Byfield, Chidiebube Ugwe, Yajur Arya, Arshi Syal, Ryan J Mayo
Journal: Blood (2024)
Outcomes of Hematopoietic Stem Cell Transplantation in Primary Plasma Cell Leukemia: A Systematic Review and Meta-Analysis
Authors: Qamar Iqbal, Sohaib Irfan, Ahmad Basharat, Prashil Dave, Ahmed Hebishy, Muhammad Kashif Amin, Muhammad Umair Mushtaq, Moazzam Shahzad
Journal: Blood (2024)
Peripheral Blood Smear-Based Deep Learning to Predict Cancer-Associated Thrombosis
Authors: Deepika Dilip, Siddharth Singi, Dylan C. Webb, Cesar Colorado-Jimenez, Rohan Singh, Zhanghan Yin, Sean Paulsen, Lauren McVoy, Maly Fenelus, Mikhail Roshal, Chad Vanderbilt, Jeffrey I. Zwicker, Ahmet Dogan, Gregory Mark Goldgof, Simon Mantha
Journal: Blood (2024)
Real-World Evidence for Duvelisib and Romidepsin Combination in Patients with Relapsed/Refractory Peripheral T-Cell Lymphomas
Authors: Josie G Ford, Sean M McCabe, Alexandra W Lenart, Mark N Sorial, Mwanasha H. Merrill, Anna B Rider, Aliyah R. Sohani, Ronald A Nemec, Kusha Chopra, Caroline MacVicar, Eric D. Jacobsen, Salvia Jain
Journal: Blood (2024)
Exploring N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) in Children with Sickle Cell Disease (SCD) and Vaso-Occlusive Pain Episodes (VOE)
Authors: Dunia Hatabah, Rawan Korman, Giorgi Maziashvili, Lou Ann Brown, Frank Harris, Chris A. Rees, Carlton Dampier, Claudia R. Morris
Journal: Blood (2024)
Variables Associated with Outcomes in Patients with Chronic Neutrophilic Leukemia with <i>CSF3RT618I</i> : A Multi-Centre Retrospective Study
Authors: Qian Jiang, Na Xu, Xiaoli Liu, Li Meng, Suning Chen, Jianyong Li, Linhua Yang, Chun-Yan Chen, Limei Chen, Jie Sun, Ling Pan, Minghui Duan, Hongmei Jing, Jinhai Ren, Fengru Lin, Xuemei Qin, Junqing Xu, Robert Peter Gale, Mingfeng Zhao, Zhilan Pan, Xianhua Yuan, Lijuan Cui, Zhijian Xiao, Li Weiming
Journal: Blood (2024)
RBC eNOS Regulates O2 Delivery Phenotype during Circulatory Transit Via Control of Intracellular pH
Authors: Stephen C Rogers, Zohreh Safari, Mary E Brummet, Daniel Bennett, Emioluwa Odunaiya, Adaora Eziemefe, Jacqueline Nguyen, Sarah Enjati, Olivia Conelius, Aaron Issaian, Monika monikA.dzieciatkow, Fabia Gamboni, Jason Held, Angelo D'Alessandro, Luke S Dunaway, Isakson Brant, Miriam Cortese Krott, Allan Doctor
Journal: Blood (2024)
Oral Vitamin C Supplementation Modulates Inflammatory Cytokines in Clonal Cytopenia of Undetermined Significance and Low-Risk Myeloid Malignancies: Results from EVI-2 Trial
Authors: Ali Al-Mousawi, Stine Ulrik Mikkelsen, Amalie Bach Nielsen, Anders Pommer Vallentin, Astrid Ø. Mortensen, Zachary Madaj, Jakob Jespersen, Linn Gillberg, Jakob Werner Hansen, Mette Klarskov Andersen, Bo Mortensen, Marianne Tang Severinsen, Casey O'Connell, Jens Lykkesfeldt, Peter A. Jones, Kirsten Gronbaek
Journal: Blood (2024)
Efficacy of the Peptide Drug Conjugates Melflufen and OPDC3 in Venetoclax Resistant Acute Myeloid Leukemia
Authors: Romika Kumari, Juho J. Miettinen, Mahesh B. Tambe, June Olgac, Tanja Ruokoranta, Nemo Ikonen, Minna H. Suvela, Maiju-Emilia Huppunen, Stefan Svensson Gelius, Klara Acs, Caroline A. Heckman
Journal: Blood (2024)
Sociodemographic and Patient-Related Determinants of Outcomes after Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GvHD Prophylaxis
Authors: Sibgha Gull Chaudhary, Moazzam Shahzad, Kayla Pfannenstiell, Muhammad Kashif Amin, Amir Kasaeian, Muhammad Fareed Khalid, Hediyeh Alemi, Naghmeh Khavandgar, Iqra Anwar, Matthew McGuirk, Syed Nasir Abbas Bukhari, Anurag K. Singh, Mehdi Hamadani, Joseph P. McGuirk, Muhammad Umair Mushtaq
Journal: Blood (2024)
The Impact of CMV-Prophylaxis with Letermovir on Immune Reconstitution after Allogeneic Stem Cell Transplantation: Single-Center Analysis of 363 Transplanted Patients
Authors: Adela Maria Neagoie, Conrad Weidt, Daniel Fürst, Verena Wais, Christian Sinzger, Katrin Strauss, Katharina Göhring, Jacqueline Schnell, Michaela Feuring, Thomas Stamminger, Hartmut Döhner, Donald Werner Bunjes, Elisa Sala
Journal: Blood (2024)
Response Adapted Dasatinib De-Escalation Strategy Compared to Upfront Low-Dose Dasatinib: A Prospective Cohort Study
Authors: Reema Singh, Sujay Rainchwar, Sakshi Bhatnagar, Nakul Tikare, Roy Palatty, Tribikram Panda, Rayaz Ahmed, Narendra Agrawal, Dinesh Bhurani, Rohan Halder
Journal: Blood (2024)
Transcription Factor Networks Disproportionately Enrich for Heritability of Blood Cell Phenotypes
Authors: Alexis Caulier, Jorge Diego Martin Rufino, Seayoung Lee, Nicole Castano, Emily King, Samantha Joubran, Marcus Joseph Jones, Seth Raphael Goldman, Uma Arora, Lara Wahlster, Eric Lander, Vijay G. Sankaran
Journal: Blood (2024)
Socioeconomic Disparities in Allogeneic Hematopoietic Cell Transplant Outcomes
Authors: Moazzam Shahzad, Zouina Sarfraz, Ben Ponvilawan, Muhammad Kashif Amin, Ankita Gupta, Matthew McGuirk, Sibgha Gull Chaudhary, Iqra Anwar, Leyla O. Shune, Joseph P. McGuirk, Mehdi Hamadani, Muhammad Umair Mushtaq
Journal: Blood (2024)
Concizumab As a Possible Treatment for Bleeding Disordersof Unknown Cause
Authors: Paula Acuña, Elena Monzón Manzano, María Teresa Alvarez-Román, Elena G Arias-Salgado, Eduardo Garcia Perez, Monica Martin Salces, Maria Isabel Rivas Pollmar, Rick Kapur, Victor Jimenez Yuste, Nora Butta
Journal: Blood (2024)
Could Somatic Gene Rescue Explain Frequency of Compound Heterozygous and Concurrent Receptor Tyrosine Kinase Mutations in Hematological Diseases?
Authors: Serhan Unlu, Christopher Haddad, Tariq Kewan, Olisaemeka Ogbue, Arda Durmaz, Waled Bahaj, Arooj Ahmed, Carlos Bravo-Perez, Luca Guarnera, Hetty E. Carraway, Yasuo Kubota, Carmelo Gurnari, Torsten Haferlach, Valeria Visconte, Jaroslaw Maciejewski
Journal: Blood (2024)
Pacritinib Therapy for JAK2 Inhibitor-Naïve or -Experienced Patients with Myelofibrosis: Mayo Clinic Series of 60 Consecutive Patients Treated Outside of Clinical Trials
Authors: Maymona Abdelmagid, Jeanne Palmer, Aref Al-Kali, Mehrdad Hefazi, James M. Foran, Kebede Begna, Cecilia Y. Arana Yi, Animesh D. Pardanani, Naseema Gangat, Ayalew Tefferi
Journal: Blood (2024)
Monocytosis Is an Independent Risk Factor for Survival in Essential Thrombocythemia - a Revised Triple-a Prognostic Score (AAA+A) Based on Age and Absolute Monocyte, Neutrophil, and Lymphocyte Counts
Authors: Ayalew Tefferi, Giuseppe Gaetano Gaetano Loscocco, Maymona Abdelmagid, Animesh D. Pardanani, Kebede Begna, Mrinal M. Patnaik, Natasha Szuber, Alessandra Carobbio, Tiziano Barbui, Kaaren K. Reichard, Paola Guglielmelli, Naseema Gangat, Alessandro M. Vannucchi
Journal: Blood (2024)
Low Dose Post-Transplant Cyclophosphamide in Combination with Alemtuzumab As Gvhd-Prophylaxis Is Associated with Improved Outcomes and Safe Side Effect Profile in HLA-Mismatched Unrelated Transplantation
Authors: Panagiotis Tsirigotis, Ioanna Lazana, Ioannis Konstantellos, Maria Stamouli, Konstantinos Gkirkas, Spiros Chondropoulos, Pinelopi Vryttia, Georgia Gkolfinopoulou, Panagiota Katsiampoura
Journal: Blood (2024)
Biallelic Deletion 13q in Chronic Lymphocytic Leukemia Treated with Targeted Agents
Authors: Malte Knöll, Rashmi Priyadharshini Dheenadayalan, Deyan Y. Yosifov, Jialei Qi, Christof Schneider, Felix Seyfried, Lueder Hinrich Meyer, Paula Cramer, Julia Von Tresckow, Michael Hallek, Barbara F. Eichhorst, Eugen Tausch, Stephan Stilgenbauer, Billy Jebaraj
Journal: Blood (2024)
Short-Term Fostamatinib Treatment Impacts Hematopoiesis and Downregulates Thromboinflammation in Townes Sickle Mice
Authors: Bindu Parachalil Gopalan, Sayuri Kamimura, Pradeep Dagur, Niharika Shah, Martha Quezado, Zenaide Quezado, Arun S. Shet
Journal: Blood (2024)
MLL5-Driven Leukemic Transformation Is Linked to Chromatin Remodeling and Can be Targeted with ATRA in Combination with PARP1 Inhibition
Authors: Luise Araujo De Albuquerque Simoes, Isabel Weinhäuser, Diego A Pereira-Martins, Luciana Yamamoto Almeida, Vincent Van Den Boom, Fatemeh Mojallali, Dominique Sternadt, Prodromos Chatzikyriakou, Xuesen Zheng, César Alexander Ortiz Rojas, Ghulam Jeelani Mufti, Lucio Henrique Pinheiro, Lynn Quek, Gerwin A. Huls, Eduardo M. Rego, Jan Jacob Schuringa
Journal: Blood (2024)
Implementation of Automated Thrombosis and Bleeding Risk Assessment in Cancer Patients Undergoing Systemic Therapy
Authors: Ang Li, Shengling Ma, Raka Bandyo, Mrinal Ranjan, Elizabeth Chiang, Joyce Tiong, Jun Yang Jiang, Justine Ryu, Omid Jafari, Christopher I Amos, Nathanael R. Fillmore, Jennifer La, Karlyn A. Martin, Chirayu J Shah, Aparna Jotwani
Journal: Blood (2024)
Chemical Modulation of ELF1 Binding to RUNX1 Target Genes Leads to Increased Hematopoietic Stem Cell Self-Renewal
Authors: Anne L. Robertson, Lu Yue, Avik Choudhuri, Caroline Kubaczka, Samuel J. Wattrus, Joseph Mandelbaum, Serine Avagyan, Song Yang, Rebecca J. Freeman, Victoria Chan, Megan C. Blair, George Q. Daley, Leonard I. Zon
Journal: Blood (2024)
Comparison of Race-neutral Versus Race-specific Spirometry Equations for Evaluation of Child Asthma
Authors: Amy L. Non, Xiuhong Li, Miranda R. Jones, Emily Oken, Tina Hartert, Nathan Schoettler, Diane R. Gold, Sima Ramratnam, Eric M. Schauberger, Kelan Tantisira, Leonard B Bacharier, Douglas J. Conrad, Kecia N Carroll, Flory L. Nkoy, Heike Luttmann-Gibson, Frank D. Gilliland, Carrie V Breton, Meyer Kattan, Robert F Lemanske, Augusto A Litonjua, Cythia T. McEvoy, Katherine Rivera-Spoljaric, Christian Rosas-Salazar, Christine L. M. Joseph, Meredith Palmore, Patrick H Ryan, Ganesa Wegienka, Alexandra R. Sitarik, Anne Marie Singh, Rachel L. Miller, Edward M. Zoratti, Dennis Ownby, Carlos A Camargo, Judy L. Aschner, Annemarie Stroustrup, Shohreh F. Farzan, Margaret R Karagas, Daniel J Jackson, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Race-based estimates of pulmonary function in children could influence the evaluation of asthma in children from racial and ethnic minoritized backgrounds.
C-reactive Protein-based Screening of People with Tuberculosis Symptoms: A Diagnostic Accuracy Study
Authors: Brigitta Derendinger, Tessa K. Mochizuki, Danaida Marcelo, Deepa Shankar, Wilson Mangeni, Hanh Nguyen, Seda Yerlikaya, William Worodria, Charles Yu, Nhung Viet Nguyen, Devasahayam Jesudas Christopher, Grant Theron, Patrick PJ Phillips, Payam Nahid, Claudia M. Denkinger, Adithya Cattamanchi, Christina Yoon
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB screening test. Methods/Measurements: Consecutive outpatient adults with cough ≥2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model. Results: Among 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (≥91%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.
Physician associates: GMC makes only small changes to regulation after consultation
Authors: Jacqui Wise
Journal: BMJ (2024)

The General Medical Council has made only minor changes to how it will regulate physician associates (PAs) and anaesthesia associates (AAs) from 13 December, after a consultation that received more than 3000 responses. The GMC said that many of the responses to the consultation, which launched in March,12 were outside the scope of the consultation or already settled in law. In its report the GMC provided a detailed summary of the feedback it received to the technical consultation.3 The main changes the regulator has made to PA and AA regulation in response to the consultation were:
Intermittent Phrenic Nerve Stimulation May Prevent Atelectasis and Ventilator-induced Diaphragm Dysfunction
Authors: Mayson L. A. Sousa, L. Felipe Damiani, Sebastian Dubo, Annia Schreiber, Clement Brault, Fernando Vieira, Catherine A Bellissimo, W. Darlene Reid, Ewan C. Goligher, Arthur S Slutsky, Martin Post, Laurent J. Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Avenues towards reconciling wild and managed bee proponents
Authors: Alexis L Beaurepaire, Katja Hogendoorn, David Kleijn, Gard W Otis, Simon G Potts, Theresa L Singer, Samuel Boff, Christian Pirk, Josef Settele, Robert J Paxton, Nigel E Raine, Simone Tosi, Neal Williams, Alexandra-Maria Klein, Yves Le Conte, Joshua W Campbell, Geoffrey R Williams, Lorenzo Marini, Axel Brockmann, Fabio Sgolastra, Natalie Boyle, Markus Neuditschko, Lars Straub, Peter Neumann, Jean-Daniel Charrière, Matthias Albrecht, Vincent Dietemann
Journal: Trends in Ecology & Evolution (2024)
Impact of Respiratory Co-Detection in Critically Ill Patients with <i>Pneumocystis jirovecii</i> Pneumonia
Authors: Ki-Ho Park, Jin Won Huh, Sang-Bum Hong, Heungsup Sung, Kyung-Hyun Do, Sang-Oh Lee, Chae-Man Lim, Younsuck Koh, Sang-Ho Choi
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Fabrication of lactoferrin-chitosan-etoposide nanoparticles with melatonin via carbodiimide coupling: In-vitro &amp; in-vivo evaluation for colon cancer
Authors: Harshvardhan Raval, Sankha Bhattacharya, Darshan Bhirud, Preeti Chidambar Sangave, Girdhari Lal Gupta, Gaurav Paraskar, Megha Jha, Satyam Sharma, Sateesh Belemkar, Devendra Kumar, Rahul Maheshwari
Journal: Journal of Controlled Release (2024)
A New Severe Congenital Neutropenia Syndrome Associated with Autosomal Recessive <i>COPZ1</i> Mutations
Authors: Natalia Borbaran Bravo, Ekaterina Deordieva, Larissa Doll, Mohammad ElGamacy, Benjamin Dannenmann, Joana Azevedo, Alberto Iannuzzo, Selket Delafontaine, Moritz Lehners, Marius Sebastian Theo Kolodziej, Birte Hernandez Alvarez, Anna-Sophia Hellmuth, Malte Ritter, Betül Findik, Viktoria Zakharova, Sandro Bräuning, Sergey Kandabarau, Claudia Lengerke, Robert Feil, Isabelle Meyts, Jérôme Delon, Markus F. Templin, Marc Sturm, Olaf Rieß, Cornelia Zeidler, Karl Welte, Anna Shcherbina, Maksim Klimiankou, Julia Skokowa
Journal: Blood (2024)
Socioeconomic status and the risk for colonisation or infection with priority bacterial pathogens: a global evidence map
Authors: Sarah Blackmon, Esther E Avendano, Nanguneri Nirmala, Courtney W Chan, Rebecca A Morin, Sweta Balaji, Lily McNulty, Samson Alemu Argaw, Shira Doron, Maya L Nadimpalli
Journal: The Lancet Microbe (2024)
Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness
Authors: Rombout B.E. van Amstel, Brian Bartek, Alexander P J Vlaar, Elizabeth Gay, Lonneke A. van Vught, Olaf L Cremer, Tom Van der Poll, Nathan I Shapiro, Michael A. Matthay, Carolyn S Calfee, Pratik Sinha, Lieuwe D. J. Bos
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.
Scurvy incidence trend among children hospitalised in France, 2015–2023: a population-based interrupted time-series analysis
Authors: Zein Assad, Maelle Trad, Zaba Valtuille, Cécile Dumaine, Albert Faye, Tania Ikowsky, Florentia Kaguelidou, Lindsay Osei, Naim Ouldali, Ulrich Meinzer
Journal: The Lancet Regional Health - Europe (2024)
A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis
Authors: Sina Bohnacker, Fiona D. R. Henkel, Franziska Hartung, Arie Geerlof, Sandra Riemer, Ulrich F. Prodjinotho, Eya Ben Salah, André Santos Dias Mourão, Stefan Bohn, Tarvi Teder, Dominique Thomas, Robert Gurke, Christiane Boeckel, Minhaz Ud-Dean, Ann-Christine König, Alessandro Quaranta, Francesca Alessandrini, Antonie Lechner, Benedikt Spitzlberger, Agnieszka M. Kabat, Edward Pearce, Jesper Z. Haeggström, Stefanie M. Hauck, Craig E. Wheelock, Per-Johan Jakobsson, Michael Sattler, David Voehringer, Matthias J. Feige, Clarissa Prazeres da Costa, Julia Esser-von Bieren
Journal: Science Immunology (2024)

The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using Heligmosomoides polygyrus bakeri ( Hpb ), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E 2 (PGE 2 ) as a major immune regulatory mechanism of heGDH. The induction of PGE 2 and other immunoregulatory factors, including IL-12 family cytokines and indoleamine 2,3-dioxygenase 1, by heGDH required p300-mediated histone acetylation, whereas the enzyme’s catalytic activity suppressed the synthesis of type 2–promoting leukotrienes by macrophages via 2-hydroxyglutarate. By contrast, the induction of immunoregulatory factors involved the heGDH N terminus by potentially mediating interactions with cellular targets (CD64 and GPNMB) identified by proteomics. Type 2 cytokines counteracted suppressive effects of heGDH on host defense, indicating that type 2 immunity can limit helminth-driven immune evasion. Thus, helminths harness a ubiquitous metabolic enzyme to epigenetically target type 2 macrophage activation and establish chronicity.
The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication
Authors: Paul J. Baker, Andrea C. Bohrer, Ehydel Castro, Eduardo P. Amaral, Maryonne Snow-Smith, Flor Torres-Juárez, Sydnee T. Gould, Artur T. L. Queiroz, Eduardo R. Fukutani, Cassandra M. Jordan, Jaspal S. Khillan, Kyoungin Cho, Daniel L. Barber, Bruno B. Andrade, Reed F. Johnson, Kerry L. Hilligan, Katrin D. Mayer-Barber
Journal: Science Immunology (2024)

Severity of COVID-19 is affected by multiple factors; however, it is not understood how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure affects the control of viral replication. Here, we demonstrate that immune events in the mouse lung closely preceding SARS-CoV-2 infection affect viral control and identify innate immune pathways that limit viral replication. Pulmonary inflammatory stimuli including resolved, antecedent respiratory infections with Staphylococcus aureus or influenza, ongoing pulmonary Mycobacterium tuberculosis infection, ovalbumin/alum-induced asthma, or airway administration of TLR ligands and recombinant cytokines all establish an antiviral state in the lung that restricts SARS-CoV-2 replication. In addition to antiviral type I interferons, TNFα and IL-1 potently precondition the lung for enhanced viral control. Our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation preceding SARS-CoV-2 exposure may contribute to variability in disease outcomes.
MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection
Authors: Huimeng Wang, Michael N. T. Souter, Marcela de Lima Moreira, Shihan Li, Yuchen Zhou, Adam G. Nelson, Jinhan Yu, Lucy J. Meehan, Bronwyn S. Meehan, Sidonia B. G. Eckle, Hyun Jae Lee, Jan Schröder, Ashraful Haque, Jeffrey Y. W. Mak, David P. Fairlie, James McCluskey, Zhongfang Wang, Zhenjun Chen, Alexandra J. Corbett
Journal: Science Immunology (2024)

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)–producing MAIT1 and interleukin-17A (IL-17A)–producing MAIT17 cell subsets in vivo. Whereas T-bet + MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt + MAIT17 cells could undergo phenotypic and functional conversion into both RORγt + T-bet + MAIT1/17 and RORγt − T-bet + MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A–secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell–targeted vaccines.