Article
Immunology
Richel J. C. Bilderbeek, Maksim V. Baranov, Geert van den Bogaart, Frans Bianchi
Summary: This study reveals the over-presentation of membrane protein fragments in cytolytic and helper T cell responses. It also demonstrates the evolutionary conservation and lower frequency of mutations in transmembrane helices, suggesting that T cells are more tuned to respond to membrane proteins to avoid evasion by pathogens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Yingying Shi, Yu Liu, Jiaxin Huang, Zhenyu Luo, Xuemeng Guo, Mengshi Jiang, Xiang Li, Yichao Lu, Xu Liu, Xinyu Shan, Lihua Luo, Jian You
Summary: This study indicates that a simultaneous and coordinated mobilization of MHC-restricted immunity may enhance cancer therapy, providing new insights for cancer treatment.
Article
Immunology
Agata Lopes-Ribeiro, Franklin Pereira Araujo, Patricia de Melo Oliveira, Lorena de Almeida Teixeira, Geovane Marques Ferreira, Alice Aparecida Lourenco, Laura Cardoso Correa Dias, Caio Wilker Teixeira, Henrique Morais Retes, Elisson Nogueira Lopes, Alice Freitas Versiani, Edel Figueiredo Barbosa-Stancioli, Flavio Guimaraes da Fonseca, Olindo Assis Martins-Filho, Moriya Tsuji, Vanessa Peruhype-Magalhaes, Jordana Grazziela Alves Coelho-dos-Reis
Summary: This study aimed to identify MHC-I-restricted peptide signatures for arboviruses using in silico and in vitro peptide microarray tools. The results showed that there were few overlapping immunogenic peptides between different arboviruses, with DENV-derived peptides showing the highest reactivity with HLA-A*02:01. Additionally, non-structural proteins were identified as hotspots for HLA-A*02:01-reactive peptides.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Maria C. Tovar Fernandez, Ewa M. Sroka, Mathilde Lavigne, Aikaterini Thermou, Chrysoula Daskalogianni, Benedicte Manoury, Rodrigo Prado Martins, Robin Fahraeus
Summary: The accumulation of protein aggregates is toxic and its relation to diseases is still unclear. This study reveals that certain antigenic peptides can be presented to the MHC class I pathway via autophagy. The presentation of peptides derived from the viral EBNA1 protein was not affected by autophagy suppression, while the presentation of ovalbumin was suppressed. The study also suggests that the relative levels of protein expression do not affect autophagy-mediated antigen presentation.
CELLULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jieru Deng, Chunni Lu, Chuanxin Liu, Sara Oveissi, W. Douglas Fairlie, Erinna F. Lee, Pamuk Bilsel, Hamsa Puthalakath, Weisan Chen
Summary: The study demonstrates that IAV infection induces endogenous presentation of a viral epitope by MHC-II to CD4(+) T cells, dependent on de novo protein synthesis and the ER-Golgi network. Some antigenic peptides are of cytosolic origin in this process. Additionally, autophagy inhibitors and deletion of autophagy-related genes block most of the MHC-II-restricted endogenous IAV antigen presentation.
Article
Oncology
Haocai Chang, Zhengzhi Zou, Jie Li, Qi Shen, Lei Liu, Xiaorui An, Sihua Yang, Da Xing
Summary: Low fluence laser therapy enhances antigen-specific immune response by upregulating MHC class II in macrophages and dendritic cells, via the activation of mitochondrial ROS signaling pathway. This treatment strategy suppresses tumor growth by altering the adaptive immune response.
Article
Biochemistry & Molecular Biology
F. Tudor Ilca, Louise H. Boyle
Summary: The glycosylation status of MHC-I molecules affects their affinity for TAPBPR, with non-glycosylated MHC-I showing stronger interactions and easier peptide exchange compared to glycosylated counterparts. TAPBPR is more resistant to peptide-mediated allosteric release from non-glycosylated MHC-I, indicating the important role of glycans in modulating protein interactions.
MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Yang Liu, Baozeng Sun, Jiawei Wang, Hao Sun, Zhenhua Lu, Longyu Chen, Mingfu Lan, Jiahao Xu, Jingyu Pan, Jingqi Shi, Yuanjie Sun, Xiyang Zhang, Jing Wang, Dongbo Jiang, Kun Yang
Summary: This study used computational approaches to predict the MHC class-I restricted epitopes of Ebola virus glycoprotein, and validated their conservation and immunogenicity. These results contribute to a better understanding of the immune response to Ebola virus and provide potential strategies for epitope-based immunotherapy.
INTERNATIONAL IMMUNOLOGY
(2022)
Article
Immunology
Bryna L. Fitzgerald, Barbara Graham, Mark J. Delorey, Adoracion Pegalajar-Jurado, M. Nurul Islam, Gary P. Wormser, John N. Aucott, Alison W. Rebman, Mark J. Soloski, John T. Belisle, Claudia R. Molins
Summary: This study used metabolomics to analyze metabolic responses in patients with Post-treatment Lyme disease symptoms/syndrome (PTLDS) compared to clinically cured non-PTLDS patients. The findings revealed observable metabolic differences between PTLDS and non-PTLDS patients at multiple time points, with distinct patterns of metabolite abundance. A small number of metabolites could be used to define PTLDS versus non-PTLDS patients at specific time points, and these findings were validated in a second patient cohort. These results suggest that metabolite-based measurement can help distinguish patients with PTLDS and provide insights into the underlying biochemistry of PTLDS.
CLINICAL INFECTIOUS DISEASES
(2021)
Review
Biology
Emily N. Gallichotte, Karen M. Dobos, Gregory D. Ebel, Mary Hagedorn, Jason L. Rasgon, Jason H. Richardson, Timothy T. Stedman, Jennifer P. Barfield
Summary: Mosquito-borne diseases are a significant burden on global public health, with efforts to control mosquitoes having both positive and negative consequences. Technological advances allow genetic manipulation of mosquitoes to increase research possibilities.
Article
Immunology
Feiyang Ma, Travis K. Hughes, Rosane M. B. Teles, Priscila R. Andrade, Bruno J. de Andrade Silva, Olesya Plazyo, Lam C. Tsoi, Tran Do, Marc H. Wadsworth, Aislyn Oulee, Maria Teresa Ochoa, Euzenir N. Sarno, M. Luisa Iruela-Arispe, Eynav Klechevsky, Bryan Bryson, Alex K. Shalek, Barry R. Bloom, Johann E. Gudjonsson, Matteo Pellegrini, Robert L. Modlin
Summary: The study identified a set of genes involved in antimicrobial responses that are differentially expressed in reversal reactions (RRs) lesions compared to lepromatous leprosy (L-lep) lesions, regulated by interferon-gamma and interleukin-1 beta. By integrating spatial coordinates of key cell types and antimicrobial gene expression, a map depicting the organized architecture of granulomas in RR and T-lep lesions was constructed, showing compositional and functional layers contributing to the antimicrobial response. Modlin and colleagues utilized single-cell RNA sequencing with cellular spatial mapping to examine the architecture of granulomas in leprosy lesions, providing insights from localized disease (tuberculoid leprosy, reversal reaction) to progressive infection (lepromatous leprosy).
Article
Dermatology
Lam C. Tsoi, Xianying Xing, Enze Xing, Rachael Wasikowski, Shuai Shao, Chang Zeng, Olesya Plazyo, Joseph Kirma, Yanyung Jiang, Allison C. Billi, Mrinal K. Sarkar, Jessica L. Turnier, Ranjitha Uppala, Kathleen M. Smith, Yolanda Helfrich, John J. Voorhees, Emanual Maverakis, Robert L. Modlin, J. Michelle Kahlenberg, Victoria E. Scott, Johann E. Gudjonsson
Summary: This study demonstrates that tape stripping with optimized high-resolution transcriptomic profiling can effectively assess and characterize inflammatory responses in the skin. By comparing different samples and sampling methods, the study shows that tape stripping can capture the transcriptome of the upper layers of the skin, providing insights into the molecular components of the immune amplification pathway in psoriasis. Additionally, the study suggests that nonlesional psoriatic skin exhibits activated, proinflammatory changes, which are not captured by full-thickness skin biopsy transcriptome profiling.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Eric R. Kehoe, Bryna L. Fitzgerald, Barbara Graham, M. Nurul Islam, Kartikay Sharma, Gary P. Wormser, John T. Belisle, Michael J. Kirby
Summary: The study developed a pipeline for data preprocessing, biomarker selection, and classification of LCMS serum samples for Lyme disease diagnosis, achieving a 98.13% test balanced success rate. The methodology is generalizable and can be adapted to other LCMS or metabolomics data sets.
SCIENTIFIC REPORTS
(2022)
Article
Microbiology
Nastassja L. Kriel, Mae Newton-Foot, Owen T. Bennion, Bree B. Aldridge, Carolina Mehaffy, John T. Belisle, Gerhard Walzl, Robin M. Warren, Samantha L. Sampson, Nico C. Gey van Pittius
Summary: In this study, the sub-cellular location of EccA(3) in mycobacteria was investigated. Time-lapse microscopy showed that EccA(3) localizes to the growing pole in M. smegmatis. The co-purification of EccA(3) with proteins involved in polar growth, mycolic acid synthesis, and secretion systems suggests that EccA(3) is located at the site of active cell growth.
Article
Cell Biology
Allison C. Billi, Feiyang Ma, Olesya Plazyo, Mehrnaz Gharaee-Kermani, Rachael Wasikowski, Grace A. Hile, Xianying Xing, Christine M. Yee, Syed M. Rizvi, Mitra P. Maz, Celine C. Berthier, Fei Wen, Lam C. Tsoi, Matteo Pellegrini, Robert L. Modlin, Johann E. Gudjonsson, J. Michelle Kahlenberg
Summary: This study analyzed the skin and circulating immune cells of lupus patients using integrated single-cell RNA sequencing and spatial RNA sequencing. The findings reveal that the normal-appearing skin of patients with lupus is characterized by an interferon-rich environment and that CD16+ dendritic cells undergo interferon education in the skin, leading to proinflammatory phenotypes. These results provide important insights into the pathogenesis of cutaneous lupus erythematosus.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Immunology
Carolina Mehaffy, Joan M. Ryan, Nicole A. Kruh-Garcia, Karen M. Dobos
Summary: Tuberculosis (TB) is a major public health issue causing millions of infections and resulting in significant death rates. Efforts to control TB include developing new vaccines, drug treatments, and diagnostic methods. Understanding the physiology of the primary causative agent, Mycobacterium tuberculosis (Mtb), is crucial for advancements in these areas.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Nicolas Gisch, Christian Utpatel, Lisa M. Gronbach, Thomas A. Kohl, Ursula Schombel, Sven Malm, Karen M. Dobos, Danny C. Hesser, Roland Diel, Udo Goetsch, Silke Gerdes, Yassir A. Shuaib, Nyanda E. Ntinginya, Celso Khosa, Sofia Viegas, Glennah Kerubo, Solomon Ali, Sahal A. Al-Hajoj, Perpetual W. Ndung'u, Andrea Rachow, Michael Hoelscher, Florian P. Maurer, Dominik Schwudke, Stefan Niemann, Norbert Reiling, Susanne Homolka
Summary: Using whole genome sequencing, we characterized the global population structure of Lineage 1 (L1) strains of Mycobacterium tuberculosis complex (MTBC) and correlated this with the synthesis of phenolic glycolipids (PGL) - known virulence factors. Our results revealed eight major L1 sub-lineages with specific mutation signatures in PGL biosynthesis genes. Furthermore, we found that strains with abolished PGL biosynthesis showed enhanced growth in human macrophages.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Joan M. Ryan, Karen M. Dobos, Nicole A. Kruh-Garcia
Summary: The role of extracellular vesicles in bacterial infection provides a new avenue for understanding microbial physiology. Mycobacterium tuberculosis extracellular vesicles play a role in host-pathogen interaction and response to environmental stress, showing potential as vaccine components. Size exclusion chromatography is an effective method for enriching Mtb extracellular vesicles, surpassing the limitations of density gradient ultracentrifugation.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Immunology
Tran H. Do, Feiyang Ma, Priscila R. Andrade, Rosane Teles, Bruno J. de Andrade Silva, Chanyue Hu, Alejandro Espinoza, Jer-En Hsu, Chun-Seok Cho, Myungjin Kim, Jingyue Xi, Xianying Xing, Olesya Plazyo, Lam C. Tsoi, Carol Cheng, Jenny Kim, Bryan D. Bryson, Alan M. O'Neill, Marco Colonna, Johann E. Gudjonsson, Eynav Klechevsky, Jun Hee Lee, Richard L. Gallo, Barry R. Bloom, Matteo Pellegrini, Robert L. Modlin
Summary: Acne, a common skin condition affecting 1 in 10 people globally, is characterized by disfiguring facial lesions. This study explored the mechanisms underlying the disease using single-cell and spatial RNA sequencing, as well as ultrahigh-resolution Seq-Scope analysis. The researchers identified TREM2 macrophages expressing lipid metabolism and proinflammatory genes near the hair follicle epithelium, which expressed squalene epoxidase. Through in vitro experiments, it was discovered that squalene induced differentiation of TREM2 macrophages, impairing their ability to kill Cutibacterium acnes. Additionally, the addition of squalene to macrophages inhibited oxidative enzymes and scavenged oxygen free radicals, providing insights into the efficacy of benzoyl peroxide in acne treatment. These findings contribute to our understanding of the role of TREM2 macrophages and unsaturated lipids in the pathogenesis of acne, as well as their similarity to atherosclerosis.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jason L. Cantera, Lorraine M. Lillis, Roger B. Peck, Emmanuel Moreau, James A. Schouten, Paul Davis, Paul K. Drain, Alfred Andama, Abraham Pinter, Masanori Kawasaki, Gunilla Kallenius, Christopher Sundling, Karen M. Dobos, Danara Flores, Delphi Chatterjee, Eileen Murphy, Olivia R. Halas, David S. Boyle
Summary: This study evaluated the performance of LAM-specific antibodies in the diagnosis of tuberculosis. The research found that the epitopes of LAM in urine are different from those in in vitro cultured LAM, leading to different antibody performance. Although several new antibody pairs showed high sensitivity to LAM, no new candidate pairs with improved performance in testing urine LAM were identified.
Article
Biology
Erin W. Meermeier, Christina L. Zheng, Jessica G. Tran, Shogo Soma, Aneta H. Worley, David Weiss, Robert L. Modlin, Gwendolyn Swarbrick, Elham Karamooz, Sharon Khuzwayo, Emily B. Wong, Marielle C. Gold, David M. Lewinsohn
Summary: Human lung-resident MAIT cells are polycytotoxic, secrete antimicrobial molecules, express genes associated with persistence, and selectively express cytokine and chemokine-related molecules. These characteristics make MAIT cells early sensors in the defense of the respiratory barrier.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Alan M. O'Neill, Marc C. Liggins, Jason S. Seidman, Tran H. Do, Fengwu Li, Kellen J. Cavagnero, Tatsuya Dokoshi, Joyce Y. Cheng, Faiza Shafiq, Tissa R. Hata, Johann E. Gudjonsson, Robert L. Modlin, Richard L. Gallo
Summary: Research has shown that adipogenic fibroblasts play a critical role in acne pathogenesis and can protect against Cutibacterium acnes infection by producing cathelicidin. The ability of C. acnes to trigger cathelicidin production in preadipocytes is dependent on TLR2. Retinoic acid (RA) treatment can suppress adipogenesis and enhance cathelicidin expression in preadipocytes, providing a potential therapeutic target for difficult-to-treat acne.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Meeting Abstract
Rheumatology
Allison Billi, Feiyang Ma, Olesya Plazyo, Grace Hile, Xianying Xing, Mehrnaz Gharaee-Kermani, Rachael Wasikowski, Lam Tsoi, Matteo Pellegrini, Robert L. Modlin, Johann Gudjonsson, J. Michelle Kahlenberg
ARTHRITIS & RHEUMATOLOGY
(2021)