scholarly journals An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryan D. Pardy ◽  
Stefanie F. Valbon ◽  
Brendan Cordeiro ◽  
Connie M. Krawczyk ◽  
Martin J. Richer
Keyword(s):  
T Cell ◽  
Zika Virus ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cross Presentation ◽  
Cell Immunity ◽  
Asian Lineage ◽  
Insight Into ◽  
Host Tissues

AbstractZika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks.

scholarly journals Mapping and Role of the CD8 + T Cell Response During Primary Zika Virus Infection in Mice

2017 ◽  
Vol 21 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Annie Elong Ngono ◽  
Edward A. Vizcarra ◽  
William W. Tang ◽  
Nicholas Sheets ◽  
Yunichel Joo ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Zika Virus ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Zika Virus Infection

scholarly journals Inefficient Cross-Presentation Limits the CD8+T Cell Response to a Subdominant Tumor Antigen Epitope

2005 ◽  
Vol 175 (2) ◽  
pp. 700-712 ◽  
Author(s):  
Pavel Otahal ◽  
Sandra C. Hutchinson ◽  
Lawrence M. Mylin ◽  
M. Judith Tevethia ◽  
Satvir S. Tevethia ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Antigen ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cross Presentation ◽  
Antigen Epitope

scholarly journals Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response

2015 ◽  
Vol 90 (6) ◽  
pp. 2830-2837 ◽  
Author(s):  
Emily A. Hemann ◽  
Louisa E. Sjaastad ◽  
Ryan A. Langlois ◽  
Kevin L. Legge
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Influenza A ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cross Presentation ◽  
Cell Responses ◽  
Presentation Pathway

ABSTRACTFollowing influenza A virus (IAV) infection, development of a robust IAV-specific CD8 T cell response is required for clearance of primary infection and enhances memory protection. Following IAV infection, plasmacytoid dendritic cells (pDC) or CD8α+DC regulate pulmonary effector CD8 T cell responses within the lung. Without this DC-T cell interaction, insufficient effector CD8 T cells are maintained in the lungs, leading to enhanced morbidity and mortality. Previous studies have demonstrated that pDC are capable of classical presentation or cross-presentation of IAV antigens and could potentially regulate IAV-specific CD8 T cell responses through either mechanism. Our results demonstrate that pDC from the lungs of donor mice infected with an IAV that is not able to replicate in hematopoietic cells (142t-IAV), unlike donor pDC isolated from the lungs of control infected mice, are not able to rescue the host IAV-specific CD8 T cell response from apoptosis. This indicates that pDC must utilize the direct presentation pathway for this rescue. This inability of pDC from 142t-IAV donors to rescue the IAV-specific CD8 T cell response is not due to differences in the overall ability of 142t-IAV to replicate within the lungs or generate defective viral genomes or to differences in levels of costimulatory molecules required for this interaction. We further demonstrate that bypassing the antigen presentation pathway by coating the 142t-IAV pDC with IAV peptide epitopes restores their ability to rescue the IAV-specific CD8 T cell response.IMPORTANCEIAV continues to be a global health burden, infecting 5 to 20% of the global population annually. Continued investigation into the mechanisms that mediate protective immune responses against IAV is important to improving current vaccination and antiviral strategies antagonistic toward IAV. Our findings presented herein demonstrate a key requirement for pDC promotion of effector CD8 T cell survival: that rather than utilizing cross-presentation, pDC must be infected and utilize the endogenous pathway for presentation of antigens to CD8 T cells duringin vivoIAV infections. This suggests that targeting presentation via the endogenous pathway in pDC could be important for the development of unique antiviral cellular therapies.

scholarly journals Wnt5A supports antigen cross-presentation and CD8 T cell activation.

2022 ◽  
Author(s):  
Tresa Rani Sarraf ◽  
Malini Sen
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Response ◽  
Antigen Processing ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Mouse Bone Marrow ◽  
Recall Response ◽  
Cross Presentation

Antigen processing, cross-presentation, and antigen-specific CD8 T cell response form part and parcel of T cell-mediated immunity. Yet, lacunae remain in our understanding of antigen processing/presentation and CD8 T cell response. Given the association of Wnt5A signaling with immune homeostasis, we evaluated the utility of Wnt5A in antigen processing, cross-presentation, and CD8 T cell activation. Using mouse bone marrow-derived dendritic cells as antigen-presenting cells and ovalbumin as a model antigen we found that Wnt5A mediated regulation of actin and proteasome dynamics is inherently associated with antigen processing. A Wnt5A-Actin-Protasome axis also contributes to antigen cross-presentation and antigen responsive CD8 T cell expansion. In concurrence with these observations, we demonstrated impaired activation of ovalbumin-specific CD8 T cells in ovalbumin immunized Wnt5A heterozygous mice as illustrated by their poor CD8 T cell recall response to ovalbumin when compared to similarly immunized wild type cohorts. Our results suggest that Wnt5A signaling-directed antigen processing/presentation could be vital for generating CD8 T cell recall response to antigen, thus shedding light on a critical parameter of immunity.

scholarly journals Prolonged antigen presentation by immune complex–binding dendritic cells programs the proliferative capacity of memory CD8 T cells

2014 ◽  
Vol 211 (8) ◽  
pp. 1637-1655 ◽  
Author(s):  
Beatriz León ◽  
André Ballesteros-Tato ◽  
Troy D. Randall ◽  
Frances E. Lund
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Acute Infection ◽  
Memory Cell ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Memory Cd8 T Cells ◽  
Cross Presentation

The commitment of naive CD8 T cells to effector or memory cell fates can occur after a single day of antigenic stimulation even though virus-derived antigens (Ags) are still presented by DCs long after acute infection is resolved. However, the effects of extended Ag presentation on CD8 T cells are undefined and the mechanisms that regulate prolonged Ag presentation are unknown. We showed that the sustained presentation of two different epitopes from influenza virus by DCs prevented the premature contraction of the primary virus-specific CD8 T cell response. Although prolonged Ag presentation did not alter the number of memory CD8 T cells that developed, it was essential for programming the capacity of these cells to proliferate, produce cytokines, and protect the host after secondary challenge. Importantly, prolonged Ag presentation by DCs was dependent on virus-specific, isotype-switched antibodies (Abs) that facilitated the capture and cross-presentation of viral Ags by FcγR-expressing DCs. Collectively, our results demonstrate that B cells and Abs can regulate the quality and functionality of a subset of antiviral CD8 T cell memory responses and do so by promoting sustained Ag presentation by DCs during the contraction phase of the primary T cell response.

scholarly journals Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8+ T Cell Epitope in Immunocompetent Mice

2017 ◽  
Vol 13 (2) ◽  
pp. e1006184 ◽  
Author(s):  
Ryan D. Pardy ◽  
Maaran M. Rajah ◽  
Stephanie A. Condotta ◽  
Nathan G. Taylor ◽  
Selena M. Sagan ◽  
...  
Keyword(s):  
T Cell ◽  
Zika Virus ◽  
Cell Response ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
T Cell Epitope ◽  
Immunocompetent Mice
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