Cross, but not direct, presentation of cell‐associated virus antigens by spleen macrophages is influenced by their differentiation state

Alatery, Attiya; Siddiqui, Sarah; Chan, Matthew; Kuś, Agnieszka; Petrof, Elaine O.; Basta, Sameh

doi:10.1038/icb.2009.90

Cited by 17 publications

(19 citation statements)

References 70 publications

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“…It is likely that the majority of the CD11c À populations are Mø that were reported to cross-present antigens in a comparable manner to DC [27,28]. Interestingly, NP396 was the best epitope to be cross-presented by the CD11c 1 cell, which confirms our observation in vitro.…”

Section: Discussionsupporting

confidence: 87%

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

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The initiation of CD8 1 T cell (CTL) immune responses can occur via cross-priming. Recent data suggested a relationship between cross-presentation and immunodominance of epitope-specific T cells. To test this association, we evaluated the efficacy of crosspresentation for several virus epitopes in vitro and examined if this can be extrapolated in vivo. Employing lymphocytic choriomeningitis virus (LCMV), we demonstrate that the cross-presentation and cross-priming of LCMV antigens were dominated by NP396, but not NP205 when analyzing the LCMV-NP. Although with LCMV-GP, cross-presentation was dominated by GP276, and cross-priming was dominated by GP33. Importantly, although NP396 was significantly more efficient than GP33 in cross-presentation, cross-priming of their specific CTL was comparable. In a subsequent virus challenge after cross-priming, GP33-specific CTL dominated the response. Accordingly, based on our data, the ability of viral epitopes to be cross-presented in vitro does not entirely reflect what would occur in cross-priming. Thus, weak cross-presenting antigens may still cross-prime an efficient CTL response depending on other in vivo elements such as the naïve T-cell precursor frequencies.

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Section: Discussionsupporting

confidence: 87%

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

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“…Viral infection induces changes of cell surface molecules related to cell death, and macrophages can recognize these changes and engulf the affected cells. It has been reported that macrophages perform efferocytosis of cells infected with the influenza (Fujimoto et al, 2000; Hashimoto et al, 2007; Shiratsuchi et al, 2000; Watanabe et al, 2005, 2002, 2004; Mukherjee et al, 2017), papilloma (Hermetet et al, 2016), and Drosophila C viruses (Nainu et al, 2015; Nonaka et al, 2017), as well as Lymphocytic choriomeningitis virus (LCMV) (Alatery et al, 2010), and Human Immunodeficiency Virus Type 1 (HIV-1) (Akbar et al, 1994). …”

Section: Introductionmentioning

confidence: 99%

Protein S and Gas6 induce efferocytosis of HIV-1-infected cells

et al. 2018

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Efferocytosis, the phagocytic clearance of apoptotic cells, can provide host protection against certain types of viruses by mediating phagocytic clearance of infected cells undergoing apoptosis. It is known that HIV-1 induces apoptosis and HIV-1-infected cells are efferocytosed by macrophages, although its molecular mechanisms are unknown. To elucidate the roles that efferocytosis of HIV-1-infected cells play in clearance of infected cells, we sought to identify molecules that mediate these processes. We found that protein S, present in human serum, and its homologue, Gas6, can mediate phagocytosis of HIV-1-infected cells by bridging receptor tyrosine kinase Mer, expressed on macrophages, to phosphatidylserine exposed on infected cells. Efferocytosis of live infected cells was less efficient than dead infected cells; however, a significant fraction of live infected cells were phagocytosed over 12 h. Our results suggest that efferocytosis not only removes dead cells, but may also contribute to macrophage removal of live virus producing cells.

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“…It is possible that TLR-L influences cross-presentation through antigen uptake as well as by altering other parameters, such as phagosomal pH through NOX2 activation (3,35). Increased NOX2 activity could exacerbate antigen degradation, which in turn reduces the amount of antigen available from cross-presentation (1,27).…”

Section: Discussionmentioning

confidence: 99%

“…NP396-specific CTLs were generated as previously described (1,5). Briefly, mice were injected with 200 PFU LCMV-WE intravenously (i.v.).…”

Section: Methodsmentioning

confidence: 99%

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CD8 ⁺ T Cell Immunodominance in Lymphocytic Choriomeningitis Virus Infection Is Modified in the Presence of Toll-Like Receptor Agonists

Siddiqui

Basta

2011

J Virol

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Currently, we have limited understanding of how Toll-like receptor (TLR) engagement by microbial products influences the immune response during a concurrent virus infection. In this study, we established that dual TLR2 plus TLR3 (designated TLR2؉3) stimulation alters the immunodominance hierarchies of lymphocytic choriomeningitis virus (LCMV) epitopes by reducing NP396-specific CD8؉ T cell responses and shifting it to a subdominant position. The shift in immunodominance occurred due to a reduction in antigen uptake and the reduced cross-presentation of NP396, a major LCMV immunodominant epitope that is efficiently cross-presented. Moreover, the altered immunodominance was dependent on TLR stimulation occurring at the site of infection. Finally, as lipopolysaccharide failed to induce the same phenomenon, the data suggest that these findings are dependent not only on the dual engagement of the TRIF/MyD88 pathways but also on how TLR agonists activate antigen-presenting cells. Taken together, our data demonstrate a novel role for TLR ligands in regulating antiviral CD8؉ T cell responses due to the regulation of the cross-presentation of cell-associated antigens. CD8 ϩ T cells are important in clearing viral infections (4, 40). Despite the molecular structural complexity of most viruses, CD8ϩ T cells respond to a small subset of viral epitopes through a process termed immunodominance (44). This mechanism allows different viral epitopes that activate CD8 ϩ T cells to various degrees to be organized into a hierarchy. Within this hierarchy, immunodominant epitopes will induce the expansion of a greater number of CD8 ϩ T cells than subdominant ones (44). Immunodominance is influenced by complex factors, which include viral load, site of infection, and the kinetics of viral protein expression (24,30,39). In addition to this, T cell-related factors, which include T cell receptor (TCR) avidity and naïve CD8 ϩ T cell precursor frequencies, also are important considerations (15,17,32).Major histocompatibility complex class I (MHC-I) antigen presentation, in which peptide affinity to MHC-I molecules and the stability of peptide-MHC complexes are two major factors, is another key event that contributes to immunodominance (44). The presentation of MHC-I antigens occurs via two pathways: direct presentation and cross-presentation. Direct presentation is the process by which infected antigenpresenting cells (APCs) present peptides derived from proteins present in their own cytosol (4, 36), whereas cross-presentation occurs when professional APCs (pAPCs) present peptides derived from exogenous antigens obtained from other infected cells (4,36).Recently, a number of reports have suggested an association between immunodominance and cross-presentation. It has been demonstrated that subdominant epitopes are weakly cross-presented compared to immunodominant epitopes (21). In another study, cross-presentation was observed only for immunodominant epitopes (22). Moreover, using the lymphocytic choriomeningitis virus (LCMV) infection model...

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Cross, but not direct, presentation of cell‐associated virus antigens by spleen macrophages is influenced by their differentiation state

Cited by 17 publications

References 70 publications

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

Protein S and Gas6 induce efferocytosis of HIV-1-infected cells

CD8 ⁺ T Cell Immunodominance in Lymphocytic Choriomeningitis Virus Infection Is Modified in the Presence of Toll-Like Receptor Agonists

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Cross, but not direct, presentation of cell‐associated virus antigens by spleen macrophages is influenced by their differentiation state

Cited by 17 publications

References 70 publications

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

Protein S and Gas6 induce efferocytosis of HIV-1-infected cells

CD8 + T Cell Immunodominance in Lymphocytic Choriomeningitis Virus Infection Is Modified in the Presence of Toll-Like Receptor Agonists

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CD8 ⁺ T Cell Immunodominance in Lymphocytic Choriomeningitis Virus Infection Is Modified in the Presence of Toll-Like Receptor Agonists