6 results on '"Barber, Daniel L."'
Search Results
2. Lethal CD4 T Cell Responses Induced by Vaccination Against Staphylococcus aureus Bacteremia.
- Author
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Karauzum, Hatice, Haudenschild, Christian C., Moore, Ian N., Mahmoudieh, Mahta, Barber, Daniel L., and Datta, Sandip K.
- Subjects
T cells ,VACCINATION ,STAPHYLOCOCCUS aureus ,BACTEREMIA ,CLINICAL trials ,IMMUNE response ,BACTEREMIA prevention ,STAPHYLOCOCCAL disease prevention ,ANIMAL experimentation ,ANIMALS ,BACTERIAL vaccines ,INTERFERONS ,MICE ,STAPHYLOCOCCAL diseases ,METHICILLIN-resistant staphylococcus aureus - Abstract
Multiple candidate vaccines against Staphylococcus aureus infections have failed in clinical trials. Analysis of a recent prematurely halted vaccine trial revealed increased mortality rates among vaccine recipients in whom postsurgical S. aureus infection developed, emphasizing the potential for induction of detrimental immune responses and the need to better understand the requirements for protective immunity against S. aureus. These failures of single-antigen vaccines have prompted ongoing development of multicomponent vaccines to target the multitude of S. aureus virulence factors. In the current study, we used lethally irradiated S. aureus as a model multicomponent vaccine and showed that vaccination of mice decreased survival in a bacteremia challenge model. These deleterious effects were due to a CD4 T-cell-dependent interferon γ response and could be prevented by inhibiting development of this response during vaccination. Our results identify the potential for vaccination to induce pathological immune responses, and they have implications for recent vaccine failures and the design of future staphylococcal vaccines. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
3. Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production.
- Author
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Costa, Pedro A. C., Leoratti, Fabiana M. S., Figueiredo, Maria M., Tada, Mauro S., Pereira, Dhelio B., Junqueira, Caroline, Soares, Irene S., Barber, Daniel L., Gazzinelli, Ricardo T., and Antonelli, Lis R. V.
- Subjects
PLASMODIUM vivax ,MALARIA ,CYTOKINES ,T cells ,IMMUNE response ,LYMPHOCYTE transformation ,CD4 antigen ,CD8 antigen ,CELL receptors ,IMMUNOLOGICAL tolerance ,PROTOZOA ,RESEARCH funding - Abstract
The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection. Our goal was to define the role of these molecules during P. vivax malaria. We demonstrate that infection triggers the expression of regulatory molecules on T cells. The pattern of expression differs in CD4(+) and CD8(+) T cells. Higher frequencies of CD4(+) express more than 1 regulatory molecule compared to CD8(+) T cells. Moreover, lower proportions of CD4(+) T cells coexpress regulatory molecules, but are still able to proliferate. Importantly, simultaneously blockade of the CLTA-4, PD-1, and T-cell immunoglobulin and mucin-3 signaling restores the cytokine production by antigen-specific cells. These data support the hypothesis that upregulation of inhibitory receptors on T cells during P. vivax malaria impairs parasite-specific T-cell effector function. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
4. Type I IFN Induction via Poly-ICLC Protects Mice against Cryptococcosis.
- Author
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Sionov, Edward, Mayer-Barber, Katrin D., Chang, Yun C., Kauffman, Keith D., Eckhaus, Michael A., Salazar, Andres M., Barber, Daniel L., and Kwon-Chung, Kyung J.
- Subjects
TYPE I interferons ,CRYPTOCOCCUS neoformans ,IMMUNE response ,CELLULAR immunity ,LABORATORY mice - Abstract
Cryptococcus neoformans is the most common cause of fungal meningoencephalitis in AIDS patients. Depletion of CD4 cells, such as occurs during advanced AIDS, is known to be a critical risk factor for developing cryptococcosis. However, the role of HIV-induced innate inflammation in susceptibility to cryptococcosis has not been evaluated. Thus, we sought to determine the role of Type I IFN induction in host defense against cryptococci by treatment of C. neoformans (H99) infected mice with poly-ICLC (pICLC), a dsRNA virus mimic. Unexpectedly, pICLC treatment greatly extended survival of infected mice and reduced fungal burdens in the brain. Protection from cryptococcosis by pICLC-induced Type I IFN was mediated by MDA5 rather than TLR3. PICLC treatment induced a large, rapid and sustained influx of neutrophils and Ly6C
high monocytes into the lung while suppressing the development of eosinophilia. The pICLC-mediated protection against H99 was CD4 T cell dependent and analysis of CD4 T cell polyfunctionality showed a reduction in IL-5 producing CD4 T cells, marginal increases in Th1 cells and dramatic increases in RORγt+ Th17 cells in pICLC treated mice. Moreover, the protective effect of pICLC against H99 was diminished in IFNγ KO mice and by IL-17A neutralization with blocking mAbs. Furthermore, pICLC treatment also significantly extended survival of C. gattii infected mice with reduced fungal loads in the lungs. These data demonstrate that induction of type I IFN dramatically improves host resistance against the etiologic agents of cryptococcosis by beneficial alterations in both innate and adaptive immune responses. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
5. Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection.
- Author
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Penaloza-MacMaster, Pablo, Barber, Daniel L., Wherry, E. John, Provine, Nicholas M., Teigler, Jeffrey E., Parenteau, Lily, Blackmore, Stephen, Borducchi, Erica N., Larocca, Rafael A., Yates, Kathleen B., Hao Shen, Haining, W. Nicholas, Sommerstein, Rami, Pinschewer, Daniel D., Ahmed, Rafi, and Barouch, Dan H.
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IMMUNOLOGY , *LYMPHOCYTIC choriomeningitis , *EFFECT of drugs on T cells , *CD4 antigen , *NATURAL immunity , *IMMUNOPATHOLOGY , *IMMUNE response , *IMMUNOLOGY of inflammation , *VACCINATION - Abstract
CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. We evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
6. Visualizing Antigen-Specific and Infected Cells in Situ Predicts Outcomes in Early Viral Infection.
- Author
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Qingsheng Li, Skinner, Pamela J., Sang-Jun Ha, Duan, Lijie, Mattila, Teresa L., Hage, Aaron, White, Cara, Barber, Daniel L., O'Mara, Leigh, Southern, Peter J., Reilly, Cavan S., Carlis, John V., Miller, Christopher J., Ahmed, Rafi, and Haase, Ashley T.
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ANTIGENS , *VIRUS diseases , *IMMUNE response , *CELLS , *HIV infections , *SIMIAN viruses , *LYMPHOCYTIC choriomeningitis virus - Abstract
In the early stages of viral infection, outcomes depend on a race between expansion of infection and the immune response generated to contain it. We combined in situ tetramer staining with in situ hybridization to visualize, map, and quantify relationships between immune effector cells and their targets in tissues. In simian immunodeficiency virus infections in macaques and lymphocytic choriomeningitis virus infections in mice, the magnitude and timing of the establishment of ah excess of effector cells versus targets were found to correlate with the extent of control and the infection outcome (i.e., control and clearance versus partial or poor control and persistent infection). This method highlights the importance of the location, timing, and magnitude of the immune response needed for a vaccine to be effective against agents of persistent infection, such as HIV-1. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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