Renee Rawson, Loan Duong, Eugene Tkachenko, Austin W T Chiang, Kevin Okamoto, Ranjan Dohil, Nathan E Lewis, Richard Kurten, Edsel M Abud, Seema S Aceves
The gastrointestinal system is a hollow organ affected by fibrostenotic diseases that cause volumetric compromise of the lumen via smooth muscle hypertrophy and fibrosis. Many of the driving mechanisms remain unclear. Yes-associated protein-1 (YAP) is a critical mechanosensory transcriptional regulator that mediates cell hypertrophy in response to elevated extracellular rigidity. In the type 2 inflammatory disorder, eosinophilic esophagitis (EoE), phospholamban (PLN) can induce smooth muscle cell hypertrophy...
February 27, 2024: Mucosal Immunology
Yuting Wu, Panrui Zhang, Tianlu Shi, Dan Cao, Wen Pan
Immunoglobulin superfamily (IgSF) members are known for their role as glycoproteins expressed on the surface of immune cells, enabling protein-protein interactions to sense external signals during immune responses. However, the functions of immunoglobulins localized within subcellular compartments have been less explored. In this study, we identified an ER-localized immunoglobulin, IgSF member 6 (IgSF6), regulates ER stress and the inflammatory response in intestinal macrophages. Igsf6 expression is sustained by microbiota and significantly upregulated upon bacterial infection...
February 20, 2024: Mucosal Immunology
Ziyin Wang, Leah F Cuthbertson, Chubicka Thomas, Hadijatou J Sallah, Lucy G Mosscrop, Haoyuan Li, Tiina Talts, Kartik Kumar, Miriam F Moffatt, John S Tregoning
Respiratory viral infections remain a major cause of hospitalisation and death worldwide. Patients with respiratory infections often lose weight. Whilst acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection induced weight loss, its mechanism is not yet completely understood. We utilised a model of CD8+ T cell-driven weight loss during Respiratory Syncytial Virus (RSV) infection to dissect the immune regulation of post-infection weight loss...
February 19, 2024: Mucosal Immunology
Jiaoyan Huang, Xin Zhang, Hongkai Xu, Liuhui Fu, Yuke Liu, Jie Zhao, Jida Huang, Zuodong Song, Mingzhao Zhu, Yang-Xin Fu, Ye-Guang Chen, Xiaohuan Guo
Chemotherapy and radiotherapy frequently lead to intestinal damage. The mechanisms governing the repair or regeneration of intestinal damage are still not fully elucidated. Intraepithelial lymphocytes (IELs) are the primary immune cells residing in the intestinal epithelial layer. However, whether IELs are involved in intestinal epithelial injury repair remains unclear. Here, we found that IELs rapidly infiltrated the intestinal crypt region and are crucial for the recovery of the intestinal epithelium post-chemotherapy...
February 8, 2024: Mucosal Immunology
Lucas M Ethgen, Christopher Pastore, Cailu Lin, Danielle R Reed, Li-Yin Hung, Bonnie Douglas, Dominic Sinker, De'Broski R Herbert, Nicole M Belle
Host defense at the mucosal interface requires collaborative interactions between diverse cell lineages. Epithelial cells damaged by microbial invaders release reparative proteins such as the Trefoil factor family (TFF) peptides that functionally restore barrier integrity. However, whether TFF peptides and their receptors also serve instructive roles for immune cell function during infection is incompletely understood. Here, we demonstrate that the intestinal trefoil factor, TFF3, restrains TH 1 cell proliferation and promotes host protective Type 2 immunity against the gastrointestinal parasitic nematode Trichuris muris...
February 7, 2024: Mucosal Immunology
Qiaochu Lin, Meggie Kuypers, Yuriy Baglaenko, Eric Cao, Kebria Hezaveh, Tijana Despot, Carolina de Amat Herbozo, Mayra Cruz Tleugabulova, Juan Mauricio Umaña, Tracy L McGaha, Dana J Philpott, Thierry Mallevaey
Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to microbe-derived glycolipid antigens. iNKT cells exert fast innate effector functions that regulate immune responses in a variety of contexts, including during infection, cancer, or inflammation. The roles these unconventional T cells play in intestinal inflammation remain poorly defined and vary based on the disease model and species. Our previous work suggested that the gut microbiota influenced iNKT cell functions during dextran sulfate sodium-induced colitis in mice...
February 6, 2024: Mucosal Immunology
Ruoxun Yu, Sijing Liu, Yan Li, Liyuan Lu, Shuoya Huang, Xinwei Chen, Yunxia Xue, Ting Fu, Jun Liu, Zhijie Li
Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using AMG-517) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, TNF-α production by MCs, eosinophil infiltration and activation, and CCL11 (eotaxin-1) expression in fibroblasts...
February 6, 2024: Mucosal Immunology
Sabryna Nantel, Salma Sheikh-Mohamed, Gary Y C Chao, Alexandra Kurtesi, Queenie Hu, Heidi Wood, Karen Colwill, Zhijie Li, Ying Liu, Laurie Seifried, Benoîte Bourdin, Allison McGeer, William R Hardy, Olga L Rojas, Tho-Alfakar Al-Aubodah, Zhiyang Liu, Mario A Ostrowski, Mark A Brockman, Ciriaco A Piccirillo, Caroline Quach, James M Rini, Anne-Claude Gingras, Hélène Decaluwe, Jennifer L Gommerman
Our understanding of the quality of cellular and humoral immunity conferred by coronavirus disease 2019 (COVID-19) vaccination alone versus vaccination plus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two dose primary series and then experienced an Omicron BT...
January 24, 2024: Mucosal Immunology
Dylan Launder, John T Dillon, Leah M Wuescher, Trevor Glanz, Nora Abdul-Aziz, Elise Mein-Chiain Yi, Julian R Naglik, Randall G Worth, Heather R Conti
The fungus Candida albicans can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets and megakaryocytes in mucosal fungal infections is almost entirely unknown. When megakaryocyte- and platelet-depleted mice were infected with OPC, the tongue showed higher fungal burden, due to decreased neutrophil accumulation. Protection depended on a distinct population of oral-resident megakaryocytes...
January 19, 2024: Mucosal Immunology
Saugata Majumder, Peng Li, Shreya Das, Tanvir Noor Nafiz, Sudeep Kumar, Guangchun Bai, Hazel Dellario, Haixin Sui, Ziqiang Guan, Roy Curtiss, Yoichi Furuya, Wei Sun
Streptococcus pneumoniae (Spn) is a common pathogen causing a secondary bacterial infection following influenza which leads to severe morbidity and mortality during seasonal and pandemic influenza. Therefore, there is an urgent need to develop bacterial vaccines that prevent severe post-influenza bacterial pneumonia. Here, an improved Yersinia pseudotuberculosis strain (designated as YptbS46) possessing an Asd+ plasmid pSMV92 could synthesize high amounts of the Spn pneumococcal surface protein A (PspA) antigen and monophosphoryl lipid A as an adjuvant...
January 10, 2024: Mucosal Immunology
Angélica M Olmo-Fontánez, Julia M Scordo, Alyssa Schami, Andreu Garcia-Vilanova, Paula A Pino, Amberlee Hicks, Richa Mishra, Diego Jose Maselli, Jay I Peters, Blanca I Restrepo, Kievershen Nargan, Threnesan Naidoo, Daniel L Clemens, Adrie J C Steyn, Vivek V Thacker, Joanne Turner, Larry S Schlesinger, Jordi B Torrelles
The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis (TB), a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated M.tb growth within human alveolar macrophages...
January 5, 2024: Mucosal Immunology
Anwari Akhter, Juan I Moliva, Abul K Azad, Angélica Olmo-Fontánez, Andreu Garcia-Vilanova, Julia M Scordo, Mikhail A Gavrilin, Phillip T Diaz, Janice J Endsley, Susan T Weintraub, Larry S Schlesinger, Mark D Wewers, Jordi B Torrelles
Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF), drive susceptibility to Mycobacterium tuberculosis (M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels, and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALF vs. control-ALF (non-HIV infected people)...
January 4, 2024: Mucosal Immunology
Taylor Eddens, Olivia B Parks, Yu Zhang, Michelle L Manni, Jean-Laurent Casanova, Masato Ogishi, John V Williams
Respiratory viral infections, including human metapneumovirus (HMPV), remain a leading cause of morbidity and mortality in neonates and infants. However, the mechanisms behind the increased sensitivity to those respiratory viral infections in neonates are poorly understood. Neonates, unlike adults, have several anti-inflammatory mechanisms in the lung, including elevated baseline expression of PD-L1, a ligand for the inhibitory receptor PD-1. We thus hypothesized that neonates would rely on PD-1:PD-L1 signaling to restrain antiviral CD8 responses...
January 2, 2024: Mucosal Immunology
Biyan Zhang, Shuting Chen, Xiangyun Yin, Caleb D McBride, Jake A Gertie, Marina Yurieva, Agata A Bielecka, Brian Hoffmann, J Travis Hinson, Jessica Grassmann, Lan Xu, Emily R Siniscalco, Arielle Soldatenko, Laura Hoyt, Julie Joseph, Elizabeth B Norton, Gowthaman Uthaman, Noah W Palm, Elise Liu, Stephanie C Eisenbarth, Adam Williams
Dedicator of cytokinesis 8 (DOCK8) mutations lead to a primary immunodeficiency associated with recurrent gastrointestinal infections and poor antibody responses but paradoxically, heightened IgE to food antigens, suggesting that DOCK8 is central to immune homeostasis in the gut. Using Dock8-deficient mice, we found that DOCK8 was necessary for mucosal IgA production to multiple T cell-dependent antigens, including peanut and cholera toxin. Yet DOCK8 was not necessary in T cells for this phenotype. Instead, B cell intrinsic DOCK8 was required for maintenance of antigen-specific IgA secreting plasma cells (PCs) in the gut lamina propria...
December 28, 2023: Mucosal Immunology
Yue Tang, Xiaoqian Feng, Chaoqun Cui, Meiping Yu, Zichao Wen, Yingying Luan, Lulu Dong, Ziying Hu, Runyun Zhang, Jie Liu, Reiko Shinkura, Koji Hase, Qing Lu, Ji-Yang Wang
Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of IgA in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced Dextran Sulfate Sodium Salt (DSS)-induced colitis...
December 13, 2023: Mucosal Immunology
Hsiang-Han Su, Chih-Mei Cheng, Yung-Ning Yang, Yu-Wei Chang, Chia-Yang Li, Shin-Ting Wu, Chia-Chi Lin, Hsin-En Wu, Jau-Ling Suen
Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s. Intranasal acrylamide exposure at nanomolar levels significantly enhanced allergen-induced or recombinant mouse interleukin-33-induced lung inflammation in C57BL/6 mice or Rag1-/- mice, respectively...
February 2024: Mucosal Immunology
Samuel Ellis, Rosie Way, Miranda Nel, Alice Burleigh, Ivan Doykov, Japhette Kembou-Ringert, Maximillian Woodall, Tereza Masonou, Katie-Marie Case, Arturo Torres Ortez, Timothy D McHugh, Antonio Casal, Laura E McCoy, Sudaxshina Murdan, Robert E Hynds, Kimberly C Gilmour, Louis Grandjean, Mario Cortina-Borja, Wendy E Heywood, Kevin Mills, Claire M Smith
SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive for COVID-19, before vaccination, between June and December 2020. The samples were categorized based on their ability to block or enhance infection using in vitro assays...
November 23, 2023: Mucosal Immunology
Zihao Liu, He Xie, Ling Li, Dan Jiang, Yuna Qian, Xinhao Zhu, Mali Dai, Yanxiao Li, Ruifen Wei, Zan Luo, Weihao Xu, Qinxiang Zheng, Jianliang Shen, Meng Zhou, Wenwen Zeng, Wei Chen
Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and proinflammatory effects emerging in the acute phase of DED...
November 23, 2023: Mucosal Immunology
Kyoko Yamazaki, Nobuhiko Kamada
The oral cavity harbors a diverse microbiota that plays a significant role in maintaining homeostasis. Disruption of this balance can lead to various oral diseases, including periodontitis. Accumulating evidence suggests a connection between periodontitis and extra-oral diseases such as cardiovascular disease, rheumatoid arthritis, obesity, and diabetes. During periodontitis, oral bacteria enter the bloodstream directly, impacting extra-oral organs. Furthermore, recent studies have uncovered another pathway, the direct oral-gut axis, where oral bacteria translocate to the gut through an enteral route, influencing gut microbiota and metabolism...
November 23, 2023: Mucosal Immunology
Dana Costigan, Joe Fenn, Sandi Yen, Nicholas Ilott, Samuel Bullers, Jessica Hale, William Greenhalf, Emily Conibear, Aleksandra Koycheva, Kieran Madon, Ishrat Jahan, Ming Huang, Anjna Badhan, Eleanor Parker, Carolina Rosadas, Kelsey Jones, Myra McClure, Richard Tedder, Graham Taylor, Kenneth J Baillie, Malcolm G Semple, Peter Jm Openshaw, Claire Pearson, Jethro Johnson, Ajit Lalvani, Emily E Thornton
The relationship between gastrointestinal tract infection, the host immune response and clinical outcome of disease is not well understood in COVID-19. We sought to understand the effect of intestinal immune responses to SARS-CoV-2 on patient outcomes including magnitude of systemic antibody induction. Combining two prospective cohort studies, ISARIC4C and INSTINCT, we acquired samples from 88 COVID-19 cases representing the full spectrum of disease severity and analysed viral RNA and host gut cytokine responses in the context of clinical and virological outcome measures...
November 21, 2023: Mucosal Immunology
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