Mucosal Immunology最新文献

{"title":"Interaction of microbiota, mucosal malignancies, and immunotherapy—Mechanistic insights","authors":"Lukas F. Mager ,&nbsp;Tim Krause ,&nbsp;Kathy D. McCoy","doi":"10.1016/j.mucimm.2024.03.007","DOIUrl":"10.1016/j.mucimm.2024.03.007","url":null,"abstract":"<div><p>The microbiome has emerged as a crucial modulator of host-immune interactions and clearly impacts tumor development and therapy efficacy. The microbiome is a double-edged sword in cancer development and therapy as both pro-tumorigenic and anti-tumorigenic bacterial taxa have been identified. The staggering number of association-based studies in various tumor types has led to an enormous amount of data that makes it difficult to identify bacteria that promote tumor development or modulate therapy efficacy from bystander bacteria. Here we aim to comprehensively summarize the current knowledge of microbiome-host immunity interactions and cancer therapy in various mucosal tissues to find commonalities and thus identify potential functionally relevant bacterial taxa. Moreover, we also review recent studies identifying specific bacteria and mechanisms through which the microbiome modulates cancer development and therapy efficacy.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 402-415"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000266/pdfft?md5=fcaad5e230d25d4930a988d7cccd8485&pid=1-s2.0-S1933021924000266-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 regulates ILC3-driven intestinal immunity and homeostasis","authors":"Nicolas Jacquelot ,&nbsp;Le Xiong ,&nbsp;Wang H.J. Cao ,&nbsp;Qiutong Huang ,&nbsp;Huiyang Yu ,&nbsp;Azin Sayad ,&nbsp;Casey J.A. Anttila ,&nbsp;Tracey M. Baldwin ,&nbsp;Peter F. Hickey ,&nbsp;Daniela Amann-Zalcenstein ,&nbsp;Pamela S. Ohashi ,&nbsp;Stephen L. Nutt ,&nbsp;Gabrielle T. Belz ,&nbsp;Cyril Seillet","doi":"10.1016/j.mucimm.2024.03.002","DOIUrl":"10.1016/j.mucimm.2024.03.002","url":null,"abstract":"<div><p>Interleukin-(IL) 22 production by intestinal group 3 innate lymphoid cells (ILC3) is critical to maintain gut homeostasis. However, IL-22 needs to be tightly controlled; reduced IL-22 expression is associated with intestinal epithelial barrier defect while its overexpression promotes tumor development. Here, using a single-cell ribonucleic acid sequencing approach, we identified a core set of genes associated with increased IL-22 production by ILC3. Among these genes, programmed cell death 1 (PD-1), extensively studied in the context of cancer and chronic infection, was constitutively expressed on a subset of ILC3. These cells, found in the crypt of the small intestine and colon, displayed superior capacity to produce IL-22. PD-1 expression on ILC3 was dependent on the microbiota and was induced during inflammation in response to IL-23 but, conversely, was reduced in the presence of Notch ligand. PD-1⁺ ILC3 exhibited distinct metabolic activity with increased glycolytic, lipid, and polyamine synthesis associated with augmented proliferation compared with their PD-1⁻ counterparts. Further, PD-1⁺ ILC3 showed increased expression of mitochondrial antioxidant proteins which enable the cells to maintain their levels of reactive oxygen species. Loss of PD-1 signaling in ILC3 led to reduced IL-22 production in a cell-intrinsic manner. During inflammation, PD-1 expression was increased on natural cytotoxicity receptor (NCR)⁻ ILC3 while deficiency in PD-1 expression resulted in increased susceptibility to experimental colitis and failure to maintain gut barrier integrity. Collectively, our findings uncover a new function of the PD-1 and highlight the role of PD-1 signaling in the maintenance of gut homeostasis mediated by ILC3 in mice.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 371-386"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000217/pdfft?md5=39c9e9f5ee203de18930f74b9b8c8cae&pid=1-s2.0-S1933021924000217-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development","authors":"Zihao Liu ,&nbsp;He Xie ,&nbsp;Ling Li ,&nbsp;Dan Jiang ,&nbsp;Yuna Qian ,&nbsp;Xinhao Zhu ,&nbsp;Mali Dai ,&nbsp;Yanxiao Li ,&nbsp;Ruifen Wei ,&nbsp;Zan Luo ,&nbsp;Weihao Xu ,&nbsp;Qinxiang Zheng ,&nbsp;Jianliang Shen ,&nbsp;Meng Zhou ,&nbsp;Wenwen Zeng ,&nbsp;Wei Chen","doi":"10.1016/j.mucimm.2023.11.008","DOIUrl":"10.1016/j.mucimm.2023.11.008","url":null,"abstract":"<div><p>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 pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4⁺ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72⁺CD11c⁺ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4⁺ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 491-507"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000910/pdfft?md5=ca16c64a73aee82ce10e872e6b3af91e&pid=1-s2.0-S1933021923000910-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic fitness of IgA+ plasma cells in the gut requires DOCK8","authors":"Biyan Zhang ,&nbsp;Shuting Chen ,&nbsp;Xiangyun Yin ,&nbsp;Caleb D. McBride ,&nbsp;Jake A. Gertie ,&nbsp;Marina Yurieva ,&nbsp;Agata A. Bielecka ,&nbsp;Brian Hoffmann ,&nbsp;J. Travis Hinson ,&nbsp;Jessica Grassmann ,&nbsp;Lan Xu ,&nbsp;Emily R. Siniscalco ,&nbsp;Arielle Soldatenko ,&nbsp;Laura Hoyt ,&nbsp;Julie Joseph ,&nbsp;Elizabeth B. Norton ,&nbsp;Gowthaman Uthaman ,&nbsp;Noah W. Palm ,&nbsp;Elise Liu ,&nbsp;Stephanie C. Eisenbarth ,&nbsp;Adam Williams","doi":"10.1016/j.mucimm.2023.12.001","DOIUrl":"10.1016/j.mucimm.2023.12.001","url":null,"abstract":"<div><p>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 <em>Dock8</em>-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. Unexpectedly, DOCK8 was not required for early B cell activation, migration, or IgA class switching. An unbiased interactome screen revealed novel protein partners involved in metabolism and apoptosis. <em>Dock8</em>-deficient IgA⁺ B cells had impaired cellular respiration and failed to engage glycolysis appropriately. These results demonstrate that maintenance of the IgA⁺ PC compartment requires DOCK8 and suggest that gut IgA⁺ PCs have unique metabolic requirements for long-term survival in the lamina propria.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 431-449"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000971/pdfft?md5=3fc5cbb06a9251e14eb8f2e4c3be6155&pid=1-s2.0-S1933021923000971-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV infection impairs the host response to Mycobacterium tuberculosis infection by altering surfactant protein D function in the human lung alveolar mucosa","authors":"Anwari Akhter ,&nbsp;Juan I. Moliva ,&nbsp;Abul K. Azad ,&nbsp;Angélica Olmo-Fontánez ,&nbsp;Andreu Garcia-Vilanova ,&nbsp;Julia M. Scordo ,&nbsp;Mikhail A. Gavrilin ,&nbsp;Phillip T. Diaz ,&nbsp;Janice J. Endsley ,&nbsp;Susan T. Weintraub ,&nbsp;Larry S. Schlesinger ,&nbsp;Mark D. Wewers ,&nbsp;Jordi B. Torrelles","doi":"10.1016/j.mucimm.2023.12.003","DOIUrl":"10.1016/j.mucimm.2023.12.003","url":null,"abstract":"<div><p>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 <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>) 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 versus control-ALF (non-HIV-infected people). We further found a deficiency of surfactant protein D (SP-D) and reduced binding of SP-D to <em>M.tb</em> that had been exposed to HIV-ALF. Primary human macrophages infected with <em>M.tb</em> exposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, based on the limited number of participants in this study, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoring <em>M.tb</em> and potentially other pulmonary infections.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 461-475"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000995/pdfft?md5=5038782cf5b1e5d8d20c0cb80bf79121&pid=1-s2.0-S1933021923000995-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139111099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway","authors":"Yunxia Xue ,&nbsp;Pengyang Xu ,&nbsp;Yu Hu ,&nbsp;Sijing Liu ,&nbsp;Ruyu Yan ,&nbsp;Shutong Liu ,&nbsp;Yan Li ,&nbsp;Jun Liu ,&nbsp;Ting Fu ,&nbsp;Zhijie Li","doi":"10.1016/j.mucimm.2024.02.009","DOIUrl":"10.1016/j.mucimm.2024.02.009","url":null,"abstract":"<div><p>Sleep deprivation (SD) has a wide range of adverse health effects. However, the mechanisms by which SD influences corneal pathophysiology and its post-wound healing remain unclear. This study aimed to examine the basic physiological characteristics of the cornea in mice subjected to SD and determine the pathophysiological response to injury after corneal abrasion. Using a multi-platform water environment method as an SD model, we found that SD leads to disturbances of corneal proliferative, sensory, and immune homeostasis as well as excessive inflammatory response and delayed repair after corneal abrasion by inducing hyperactivation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Pathophysiological changes in the cornea mainly occurred through the activation of the IL-17 signaling pathway. Blocking both adrenergic and glucocorticoid synthesis and locally neutralizing IL-17A significantly improved corneal homeostasis and the excessive inflammatory response and delay in wound repair following corneal injury in SD-treated mice. These results indicate that optimal sleep quality is essential for the physiological homeostasis of the cornea and its well-established repair process after injury. Additionally, these observations provide potential therapeutic targets to ameliorate SD-induced delays in corneal wound repair by inhibiting or blocking the activation of the stress system and its associated IL-17 signaling pathway.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 323-345"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000187/pdfft?md5=7f86074878fe6227aa9a8ccfc2a8589a&pid=1-s2.0-S1933021924000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease","authors":"Melanie R. Neeland ,&nbsp;Liam Gubbels ,&nbsp;Anson Tsz Chun Wong ,&nbsp;Hannah Walker ,&nbsp;Sarath C. Ranganathan ,&nbsp;Shivanthan Shanthikumar","doi":"10.1016/j.mucimm.2024.03.001","DOIUrl":"10.1016/j.mucimm.2024.03.001","url":null,"abstract":"<div><p>Suppurative lung disease and wheezing are common respiratory diseases of childhood, however, due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and chronic suppurative lung disease for identification of endotypes that can inform improved clinical management. We used clinical microbiology data, highly multiplexed flow cytometry and immunoassays to compare pulmonary [bronchoalveolar lavage (BAL)] and systemic immunity in children with lung disease and controls. Unsupervised analytical approaches were applied to BAL immune data to explore biological endotypes. We identified two endotypes that were analogous in both frequency and immune signature across both respiratory diseases. The hyper-inflammatory endotype had a 12-fold increase in neutrophil infiltration and upregulation of 14 soluble signatures associated with type 2 inflammation and cell recruitment to tissue. The non-inflammatory endotype was not significantly different from controls. We showed these endotypes are measurable in a clinical setting and can be defined by measuring only three immune factors in BAL. We identified hyper-inflammatory and non-inflammatory endotypes common across pediatric wheeze and chronic suppurative lung disease that, if validated in future studies, have the potential to inform clinical management.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 359-370"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000205/pdfft?md5=195478082c90fee15472a0be587e30e1&pid=1-s2.0-S1933021924000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation","authors":"Yue Tang ,&nbsp;Xiaoqian Feng ,&nbsp;Qing Lu ,&nbsp;Chaoqun Cui ,&nbsp;Meiping Yu ,&nbsp;Zichao Wen ,&nbsp;Yingying Luan ,&nbsp;Lulu Dong ,&nbsp;Ziying Hu ,&nbsp;Runyun Zhang ,&nbsp;Chunhui Lu ,&nbsp;Jie Liu ,&nbsp;Reiko Shinkura ,&nbsp;Koji Hase ,&nbsp;Ji-Yang Wang","doi":"10.1016/j.mucimm.2023.12.002","DOIUrl":"10.1016/j.mucimm.2023.12.002","url":null,"abstract":"<div><p>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 immunoglobulin (Ig)A 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. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in <em>Mzb1^−/−</em> mice compared with <em>Mzb1^+/+</em> mice. The increase in CRC development and progression in <em>Mzb1^−/−</em> mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing <em>Mzb1^+/+</em> and <em>Mzb1^−/−</em> mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 450-460"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000983/pdfft?md5=f327a9bb788a4aabc854cec0d5849fba&pid=1-s2.0-S1933021923000983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 signaling in neonates restrains CD8+ T cell function and protects against respiratory viral immunopathology","authors":"Taylor Eddens ,&nbsp;Olivia B. Parks ,&nbsp;Yu Zhang ,&nbsp;Michelle L. Manni ,&nbsp;Jean-Laurent Casanova ,&nbsp;Masato Ogishi ,&nbsp;John V. Williams","doi":"10.1016/j.mucimm.2023.12.004","DOIUrl":"10.1016/j.mucimm.2023.12.004","url":null,"abstract":"<div><p>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 programmed death ligand 1 (PD-L1), a ligand for the inhibitory receptor programmed cell death protein 1 (PD-1). We thus hypothesized that neonates would rely on PD-1:PD-L1 signaling to restrain antiviral CD8 responses. To test this, we developed a neonatal primary HMPV infection model using wild-type C57BL/6 (B6) and <em>Pdcd1^-/-</em> (lacking PD-1) mice. HMPV-infected neonatal mice had increased PD-L1/PD-L2 co-expression on innate immune cells but a similar number of antigen-specific CD8⁺ T cells and upregulation of PD-1 to that of adult B6 mice. Neonatal CD8⁺ T cells had reduced interferon‐gamma (IFN-γ), granzyme B, and interleukin-2 production compared with B6 adults. <em>Pdcd1^-/-</em> neonatal CD8⁺ T cells had markedly increased production of IFN-γ and granzyme B compared with B6 neonates. <em>Pdcd1^-/-</em> neonates had increased acute pathology with HMPV or influenza. <em>Pdcd1^-/-</em> neonates infected with HMPV had long-term changes in pulmonary physiology with evidence of immunopathology and a persistent CD8⁺ T-cell response with increased granzyme B production. Using single-cell ribonucleic acid sequencing from a child lacking PD-1 signaling, a similar activated CD8⁺ T-cell signature with increased granzyme B expression was observed. These data indicate that PD-1 signaling critically limits CD8⁺ T-cell effector functions and prevents immunopathology in response to neonatal respiratory viral infections.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 3","pages":"Pages 476-490"},"PeriodicalIF":8.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923001009/pdfft?md5=168417d5ea6fad75ba7a7b54af14ef00&pid=1-s2.0-S1933021923001009-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bacterial vesicle-based pneumococcal vaccine against influenza-mediated secondary Streptococcus pneumoniae pulmonary infection","authors":"Saugata Majumder ,&nbsp;Peng Li ,&nbsp;Shreya Das ,&nbsp;Tanvir Noor Nafiz ,&nbsp;Sudeep Kumar ,&nbsp;Guangchun Bai ,&nbsp;Hazel Dellario ,&nbsp;Haixin Sui ,&nbsp;Ziqiang Guan ,&nbsp;Roy Curtiss 3rd ,&nbsp;Yoichi Furuya ,&nbsp;Wei Sun","doi":"10.1016/j.mucimm.2024.01.002","DOIUrl":"10.1016/j.mucimm.2024.01.002","url":null,"abstract":"<div><p><em>Streptococcus pneumoniae</em> (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 <em>Yersinia pseudotuberculosis</em> 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. The recombinant strain produced outer membrane vesicles (OMVs) enclosing a high amount of PspA protein (designated as OMV-PspA). A prime-boost intramuscular immunization with OMV-PspA induced both memory adaptive and innate immune responses in vaccinated mice, reduced the viral and bacterial burden, and provided complete protection against influenza-mediated secondary Spn infection. Also, the OMV-PspA immunization afforded significant cross-protection against the secondary Spn A66.1 infection and long-term protection against the secondary Spn D39 challenge. Our study implies that an OMV vaccine delivering Spn antigens can be a new promising pneumococcal vaccine candidate.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 169-181"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000023/pdfft?md5=580daefb21e141765e4fc122d099a1de&pid=1-s2.0-S1933021924000023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}