8 results on '"Barber, Daniel L."'
Search Results
2. Innate and Adaptive Interferons Suppress IL-1α and IL-1β Production by Distinct Pulmonary Myeloid Subsets during Mycobacterium tuberculosis Infection
- Author
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Mayer-Barber, Katrin D., Andrade, Bruno B., Barber, Daniel L., Hieny, Sara, Feng, Carl G., Caspar, Patricia, Oland, Sandy, Gordon, Siamon, and Sher, Alan
- Subjects
- *
INTERLEUKIN-1 , *NATURAL immunity , *INTERFERONS , *MYCOBACTERIUM tuberculosis , *MYCOBACTERIAL diseases , *CELLULAR signal transduction , *CELL differentiation , *CELLULAR immunity - Abstract
Summary: Interleukin-1 (IL-1) receptor signaling is necessary for control of Mycobacterium tuberculosis (Mtb) infection, yet the role of its two ligands, IL-1α and IL-1β, and their regulation in vivo are poorly understood. Here, we showed that both IL-1α and IL-1β are critically required for host resistance and identified two multifunctional inflammatory monocyte-macrophage and DC populations that coexpressed both IL-1 species at the single-cell level in lungs of Mtb-infected mice. Moreover, we demonstrated that interferons (IFNs) played important roles in regulating IL-1 production by these cells in vivo. Type I interferons inhibited IL-1 production by both subsets whereas CD4+ T cell-derived IFN-γ selectively suppressed monocyte-macrophages. These data provide a cellular basis for both the anti-inflammatory effects of IFNs and probacterial functions of type I IFNs during Mtb infection and reveal differential regulation of IL-1 production by distinct cell populations as an additional layer of complexity in the activity of IL-1 in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
3. Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
- Author
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Wherry, E. John, Ha, Sang-Jun, Kaech, Susan M., Haining, W. Nicholas, Sarkar, Surojit, Kalia, Vandana, Subramaniam, Shruti, Blattman, Joseph N., Barber, Daniel L., and Ahmed, Rafi
- Subjects
- *
LYMPHOCYTES , *T cells , *VIRUS diseases , *IMMUNOLOGY - Abstract
Summary: Chronic viral infections often result in T cell exhaustion. To determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells from chronic infection to functional LCMV-specific effector and memory CD8+ T cells generated after acute infection. These data showed that exhausted CD8+ T cells: (1) overexpressed several inhibitory receptors, including PD-1, (2) had major changes in T cell receptor and cytokine signaling pathways, (3) displayed altered expression of genes involved in chemotaxis, adhesion, and migration, (4) expressed a distinct set of transcription factors, and (5) had profound metabolic and bioenergetic deficiencies. T cell exhaustion was progressive, and gene-expression profiling indicated that T cell exhaustion and anergy were distinct processes. Thus, functional exhaustion is probably due to both active suppression and passive defects in signaling and metabolism. These results provide a framework for designing rational immunotherapies during chronic infections. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
4. Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.
- Author
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Le Nouën C, Nelson CE, Liu X, Park HS, Matsuoka Y, Luongo C, Santos C, Yang L, Herbert R, Castens A, Moore IN, Wilder-Kofie T, Moore R, Walker A, Zhang P, Lusso P, Johnson RF, Garza NL, Via LE, Munir S, Barber DL, and Buchholz UJ
- Subjects
- Animals, Humans, Antibodies, Neutralizing, Antibodies, Viral, Macaca mulatta, SARS-CoV-2 genetics, COVID-19 Vaccines, COVID-19 prevention & control
- Abstract
Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4
+ and CD8+ T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine., Competing Interests: Declaration of interests X.L., C.L., C.L.N., S.M., and U.J.B. are inventors on the provisional patent application number 63/180,534, entitled “recombinant chimeric B/HPIV3 expressing SARS-CoV-2 spike protein and its use,” filed by the United States Department of Health and Human Services., (Published by Elsevier Inc.)- Published
- 2022
- Full Text
- View/download PDF
5. Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection.
- Author
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Bohrer AC, Castro E, Tocheny CE, Assmann M, Schwarz B, Bohrnsen E, Makiya MA, Legrand F, Hilligan KL, Baker PJ, Torres-Juarez F, Hu Z, Ma H, Wang L, Niu L, Wen Z, Lee SH, Kamenyeva O, Kauffman KD, Donato M, Sher A, Barber DL, Via LE, Scriba TJ, Khatri P, Song Y, Wong KW, Bosio CM, Klion AD, and Mayer-Barber KD
- Subjects
- Animals, Eosinophils metabolism, Humans, Lung pathology, Macrophages, Alveolar, Mice, Receptors, G-Protein-Coupled metabolism, Mycobacterium tuberculosis physiology, Tuberculosis pathology
- Abstract
Influx of eosinophils into the lungs is typically associated with type II responses during allergy and fungal and parasitic infections. However, we previously reported that eosinophils accumulate in lung lesions during type I inflammatory responses to Mycobacterium tuberculosis (Mtb) in humans, macaques, and mice, in which they support host resistance. Here we show eosinophils migrate into the lungs of macaques and mice as early as one week after Mtb exposure. In mice this influx is CCR3 independent and instead requires cell-intrinsic expression of the oxysterol receptor GPR183, which is highly expressed on human and macaque eosinophils. Murine eosinophils interact directly with bacilli-laden alveolar macrophages, which upregulate the oxysterol-synthesizing enzyme Ch25h, and eosinophil recruitment is impaired in Ch25h-deficient mice. Our findings show that eosinophils are among the earliest cells from circulation to sense and respond to Mtb infection of alveolar macrophages and reveal a role for GPR183 in the migration of eosinophils into lung tissue., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
6. CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection.
- Author
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Foreman TW, Nelson CE, Kauffman KD, Lora NE, Vinhaes CL, Dorosky DE, Sakai S, Gomez F, Fleegle JD, Parham M, Perera SR, Lindestam Arlehamn CS, Sette A, Brenchley JM, Queiroz ATL, Andrade BB, Kabat J, Via LE, and Barber DL
- Subjects
- Animals, CD4-Positive T-Lymphocytes, Granuloma pathology, Macaca mulatta, Coinfection pathology, HIV Infections complications, HIV Infections pathology, Simian Acquired Immunodeficiency Syndrome complications, Simian Acquired Immunodeficiency Syndrome pathology, Simian Immunodeficiency Virus, Tuberculosis pathology
- Abstract
HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection., Competing Interests: Declaration of interests The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government. The authors declare no competing interests., (Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
7. Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis.
- Author
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Sallin MA, Sakai S, Kauffman KD, Young HA, Zhu J, and Barber DL
- Subjects
- Animals, Antigens, Bacterial immunology, Clone Cells, Cross-Priming immunology, Host-Pathogen Interactions immunology, Interferon-gamma metabolism, Interleukin-12 metabolism, Interleukin-12 Subunit p40 metabolism, Mice, Mycobacterium tuberculosis physiology, T-Box Domain Proteins, Tuberculosis microbiology, Cell Differentiation, Th1 Cells cytology, Th1 Cells immunology, Tuberculosis immunology, Tuberculosis pathology
- Abstract
Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73
+ CXCR3+ T-betdim stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL- 12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1+ KLRG1+ Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69+ CD103+ tissue resident phenotype effectors in lung. In contrast, Th1-cell-derived IFN-γ inhibits the accumulation of intravascular CX3CR1+ KLRG1+ Th1 cells. Thus, although IL-12 and T-bet are essential host survival factors, they simultaneously oppose lung CD4 T cell responses at several levels, demonstrating the dual nature of Th1 polarization in tuberculosis., (Published by Elsevier Inc.)- Published
- 2017
- Full Text
- View/download PDF
8. Molecular signature of CD8+ T cell exhaustion during chronic viral infection.
- Author
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Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, and Ahmed R
- Subjects
- Animals, CD8-Positive T-Lymphocytes cytology, Cell Differentiation immunology, Chronic Disease, Clonal Anergy, Female, Flow Cytometry, Gene Expression Profiling, Lymphocyte Activation genetics, Lymphocyte Activation immunology, Lymphocytic choriomeningitis virus immunology, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Phenotype, CD8-Positive T-Lymphocytes immunology, Gene Expression immunology, Immunologic Memory genetics, Virus Diseases immunology
- Abstract
Chronic viral infections often result in T cell exhaustion. To determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells from chronic infection to functional LCMV-specific effector and memory CD8(+) T cells generated after acute infection. These data showed that exhausted CD8(+) T cells: (1) overexpressed several inhibitory receptors, including PD-1, (2) had major changes in T cell receptor and cytokine signaling pathways, (3) displayed altered expression of genes involved in chemotaxis, adhesion, and migration, (4) expressed a distinct set of transcription factors, and (5) had profound metabolic and bioenergetic deficiencies. T cell exhaustion was progressive, and gene-expression profiling indicated that T cell exhaustion and anergy were distinct processes. Thus, functional exhaustion is probably due to both active suppression and passive defects in signaling and metabolism. These results provide a framework for designing rational immunotherapies during chronic infections.
- Published
- 2007
- Full Text
- View/download PDF
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