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D Lapuente, M Storcksdieck Genannt Bonsmann, A Maaske, V Stab, V Heinecke, K Watzstedt, R Heß, A M Westendorf, W Bayer, C Ehrhardt, M Tenbusch
A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies...
March 15, 2018: Mucosal Immunology
Anne Dommaschk, Lara F Lang, Regina Maus, Jennifer Stolper, Tobias Welte, Ulrich A Maus
Nasopharyngeal colonization with Streptococcus pneumoniae (the pneumococcus) is known to mount protective adaptive immune responses in rodents and humans. However, the cellular response of the nasopharyngeal compartment to pneumococcal colonization and its importance for the ensuing adaptive immune response is only partially defined. Here we show that nasopharyngeal colonization with S. pneumoniae triggered substantial expansion of both integrin αE (CD103) positive dendritic cells (DC) and T lymphocytes in nasopharynx, nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) of WT mice...
March 15, 2018: European Journal of Immunology
Rachel Mak'Anyengo, Peter Duewell, Cornelia Reichl, Christine Hörth, Hans-Anton Lehr, Sandra Fischer, Thomas Clavel, Gerald Denk, Simon Hohenester, Sebastian Kobold, Stefan Endres, Max Schnurr, Christian Bauer
Inflammatory bowel disease (IBD) is associated with enhanced levels of the IL-1 family cytokines IL-1β and IL-18, which are activated by the Nlrp3 inflammasome. Here, we investigated the role of inflammasome-driven cytokine release on T cell polarization and DC differentiation in steady state and T cell transfer colitis. In vitro and in vivo data showed that IL-1β induces Th17 polarization and increases GM‑CSF production by T cells. Reduced IL-1β levels in Nlrp3-/- mice correlated with enhanced FLT3L levels and increased frequency of tolerogenic CD103+ DC...
March 8, 2018: JCI Insight
Renan Aguilar-Valenzuela, Jason Netland, Young-Jin Seo, Michael J Bevan, Arash Grakoui, Mehul S Suthar
The mouse model of West Nile virus, which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8+ T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR) transgenic mouse with specificity to the immunodominant epitope in the WNV NS4B protein (herein referred to as transgenic WNV-I mice)...
March 7, 2018: Journal of Virology
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Nardhy Gomez-Lopez, Roberto Romero, Yi Xu, Derek Miller, Yaozhu Leng, Bogdan Panaitescu, Pablo Silva, Jonathan Faro, Ali Alhousseini, Navleen Gill, Sonia S Hassan, Chaur-Dong Hsu
PROBLEM: The immune cellular composition of amniotic fluid is poorly understood. Herein, we determined: 1) the immunophenotype of amniotic fluid immune cells during the second and third trimester in the absence of intra-amniotic infection/inflammation; 2) whether amniotic fluid T cells and ILCs display different phenotypical characteristics to that of peripheral cells; and 3) whether the amniotic fluid immune cells are altered in women with intra-amniotic infection/inflammation. METHOD OF STUDY: Amniotic fluid samples (n = 57) were collected from 15 to 40 weeks of gestation in women without intra-amniotic infection/inflammation...
March 3, 2018: American Journal of Reproductive Immunology: AJRI
Ivo S Hansen, Lisette Krabbendam, Jochem H Bernink, Fabricio Loayza-Puch, Willianne Hoepel, Johan A van Burgsteden, Elsa C Kuijper, Christianne J Buskens, Willem A Bemelman, Sebastiaan A J Zaat, Reuven Agami, Gestur Vidarsson, Gijs R van den Brink, Esther C de Jong, Manon E Wildenberg, Dominique L P Baeten, Bart Everts, Jeroen den Dunnen
CD103+ dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after bacterial infection of the lamina propria, are important for the induction of inflammation by the human CD103+ SIRPα+ DC subset. IgA-IC, by recognition through FcαRI, selectively amplify the production of proinflammatory cytokines TNF, IL-1β and IL-23 by human CD103+ DCs...
February 28, 2018: Nature Communications
Leticia Tordesillas, M Cecilia Berin
Oral tolerance is a state of systemic unresponsiveness that is the default response to food antigens in the gastrointestinal tract, although immune tolerance can also be induced by other routes, such as the skin or inhalation. Antigen can be acquired directly by intestinal phagocytes, or pass through enterocytes or goblet cell-associated passages prior to capture by dendritic cells (DCs) in the lamina propria. Mucin from goblet cells acts on DCs to render them more tolerogenic. A subset of regulatory DCs expressing CD103 is responsible for delivery of antigen to the draining lymph node and induction of Tregs...
February 27, 2018: Clinical Reviews in Allergy & Immunology
Yeon Duk Woo, Jaemoon Koh, Hye-Ryun Kang, Hye Young Kim, Doo Hyun Chung
BACKGROUND: The XCL1-XCR1 axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in allergic asthma. OBJECTIVE: In the present study, we explored that the iNKT cell-mediated XCL1-XCR1 axis regulated the allergic asthma. METHODS: Ovalbumin (OVA) or house dust mite (HDM)-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice. RESULTS: XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103+ dendritic cells (DCs), and Th2 responses in the lungs compared with wild-type (WT) mice during OVA or HDM-induced asthma...
February 20, 2018: Journal of Allergy and Clinical Immunology
Meghan E Rebuli, Erica A Pawlak, Dana Walsh, Elizabeth M Martin, Ilona Jaspers
Natural killer (NK) cells are members of the innate lymphoid cells group 1 (ILC1s), which play a critical role in innate host defense against viruses and malignancies. While many studies have examined the role of circulating peripheral blood (PB) CD56+ NK cells, little is known about the resident CD56+ cell population. Therefore, matched CD56+ cells from nasal lavage fluid (NLF) and PB of smokers and non-smokers were compared phenotypically, via flow cytometry, and functionally, via NK-cell specific gene expression...
February 21, 2018: Scientific Reports
Marta Rodriguez-Garcia, Jared M Fortier, Fiona D Barr, Charles R Wira
As women age, susceptibility to systemic and genital infections increases. Tissue-resident memory T cells (TRMs) are CD103+ CD8+ long-lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8+ T cells. While CD103+ CD8+ T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103+ CD8+ T cells were increased in postmenopausal compared to premenopausal women...
February 18, 2018: Aging Cell
Sean R McMaster, Alexander N Wein, Paul R Dunbar, Sarah L Hayward, Emily K Cartwright, Timothy L Denning, Jacob E Kohlmeier
Resident memory CD8 T (TRM ) cells in the lung parenchyma (LP) and airways provide heterologous protection against influenza virus challenge. However, scant knowledge exists regarding factors necessary to establish and maintain lung CD8 TRM . Here we demonstrate that, in contrast to mechanisms described for other tissues, airway, and LP CD8 TRM establishment requires cognate antigen recognition in the lung. Systemic effector CD8 T cells could be transiently pulled into the lung in response to localized inflammation, however these effector cells failed to establish tissue residency unless antigen was present in the pulmonary environment...
February 16, 2018: Mucosal Immunology
Peiliang Wang, Bing Huang, Yi Gao, Jianjian Yang, Zhihui Liang, Ni Zhang, Xiangning Fu, Lequn Li
CD103 + CD8 + tumor infiltrating lymphocytes (TILs) have been linked to prolonged survival in various types of cancer including non-small cell lung cancer (NSCLC). However, the factors associated with the retention of CD103 + CD8 + TILs in lung cancer tissues remain largely unknown. Additionally, the contribution of CD103 + CD8 + TILs to effective PD-1 based immunotherapy has not been fully elucidated. In this study, we identified that the expression levels of E-cadherin and TGF-β were significantly correlated with the distribution and the density of CD103 + TILs in lung cancer tumor tissues...
February 7, 2018: Cellular Immunology
Michelle L McCully, Kristin Ladell, Robert Andrews, Rhiannon E Jones, Kelly L Miners, Laureline Roger, Duncan M Baird, Mark J Cameron, Zita M Jessop, Iain S Whitaker, Eleri L Davies, David A Price, Bernhard Moser
Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8- skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1)...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Irene Soleto, Uwe Fischer, Carolina Tafalla, Aitor G Granja
Dendritic cells (DCs) are highly specialized antigen-presenting cells that bridge innate and adaptive immune responses in vertebrates, being key modulators in the initiation of specific responses. Although teleost fish present the main elements of a fully developed adaptive immune system, not many studies have focused on identifying specific DC subsets in teleost species. Previous work from our group identified in rainbow trout (Oncorhynchus mykiss) skin a DC subpopulation co-expressing CD8α and major histocompatibility complex II β on the cell surface...
2018: Frontiers in Immunology
Susan van Aalst, Manon A A Jansen, Irene S Ludwig, Ruurd van der Zee, Willem van Eden, Femke Broere
Most traditional vaccines are administered via the intramuscular route. Other routes of administration however, can induce equal or improved protective memory responses and might provide practical advantages such as needle-free immunization, dose sparing and induction of tissue-specific (mucosal) immunity. Here we explored the differences in immunological outcome after immunization with model antigens via two promising immunization routes (intradermal and intranasal) with or without the experimental adjuvant and TLR7/8-agonist R848...
February 3, 2018: Vaccine
Katie L Reagin, Kimberly D Klonowski
The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM) cells residing in the lung and lung airways...
2018: Frontiers in Immunology
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
Frederick Allen, Iuliana D Bobanga, Peter Rauhe, Deborah Barkauskas, Nathan Teich, Caryn Tong, Jay Myers, Alex Y Huang
Inflammatory chemokines are critical contributors in attracting relevant immune cells to the tumor microenvironment and driving cellular interactions and molecular signaling cascades that dictate the ultimate outcome of host anti-tumor immune response. Therefore, rational application of chemokines in a spatial-temporal dependent manner may constitute an attractive adjuvant in immunotherapeutic approaches against cancer. Existing data suggest that the macrophage inflammatory protein (MIP)-1 family and related proteins, consisting of CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES), can be major determinant of immune cellular infiltration in certain tumors through their direct recruitment of antigen presenting cells, including dendritic cells (DCs) to the tumor site...
2018: Oncoimmunology
Miriam Bermudez-Brito, Theo Borghuis, Catherine Daniel, Bruno Pot, Bart J de Haan, Marijke M Faas, Paul de Vos
Probiotics such as L. plantarum WCFS1 can modulate immune responses in healthy subjects but how this occurs is still largely unknown. Immune-sampling in the Peyer Patches has been suggested to be one of the mechanisms. Here we studied the systemic and intestinal immune effects in combination with a trafficking study through the intestine of a well-established immunomodulating probiotic, i.e. L. plantarum WCFS1. We demonstrate that not more than 2-3 bacteria were sampled and in many animals not any bacterium could be found in the PP...
January 29, 2018: Scientific Reports
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