Impact of macrophage and dendritic cell subset elimination on antiviral immunity, viral clearance and production of type 1 interferon

Ciavarra, Richard P.; Taylor, Lisa D.; Greene, A. R.; Yousefieh, Nazita; Horeth, D. R.; Rooijen, Nico van; Steel, Christina; Gregory, Betsy; Birkenbach, Mark; Sekellick, Margaret J.

doi:10.1016/j.virol.2005.07.031

Cited by 43 publications

(41 citation statements)

References 38 publications

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“…production is consistent with loss of this response following liposome-mediated suicide of phagocytic cells (32). Furthermore, a recent report demonstrated that both Ag-pulsed macrophages and DCs activate and induce effector functions in naive T cells upon adoptive transfer in vivo.…”

Section: Discussionsupporting

confidence: 80%

“…In contrast, viral clearance is impaired in mice depleted of both splenic macrophages and DCs even though serum titers of type I IFN are within normal ranges (32). These different outcomes may be due to efficient clearance of VSV by splenic macrophages present in Tg mice rendered deficient of DCs but not macrophages.…”

Section: Discussionmentioning

confidence: 97%

“…This would suppress production of CD4-derived cytokines such as IL-2 and IL-4 necessary for T cell proliferation (32). However, the frequency of splenic cytokine-producing Th1 (IL-2, IFN-␥) and Th2 (IL-4) cells detected ex vivo was not diminished in Tg mice treated with DT.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, VSV disseminates to multiple organs and replicates to high titers in these mice, whereas control mice rapidly clear this virus 48 h postinfection (p.i.) (32).…”

mentioning

confidence: 99%

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Evaluation of Immunological Paradigms in a Virus Model: Are Dendritic Cells Critical for Antiviral Immunity and Viral Clearance?

Ciavarra

Stephens

Nagy

et al. 2006

The Journal of Immunology

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We have examined the role of dendritic cells (DCs) in the antiviral immune response and viral clearance using a transgenic mouse model (CD11c-diphtheria toxin (DT) receptor GFP) that allows for their conditional ablation in vivo. DT administration systemically ablated conventional and IFN-producing plasmacytoid DCs (pDCs) in transgenic, but not nontransgenic littermates, without elimination of splenic macrophages. Unexpectedly, early (12 and 48 h postinfection) viral clearance of vesicular stomatitis virus was normal in DC-depleted mice despite markedly reduced serum titers of type I IFN. DC-depleted mice remained virus-free with the exception of a subset (∼30%) that developed overwhelming and fatal brain infections 6 days postinfection. However, DT treatment profoundly inhibited clonal expansion of naive CD8+ vesicular stomatitis virus-specific T cells without altering the primary Th1 and Th2 cytokine response. Optimal clonal expansion required pDCs because selective elimination of these cells in vivo with a depleting Ab also suppressed expansion of tetramer+ cells, although Th1/Th2 cytokine production remained unaltered. Collectively, these data indicate that conventional DCs and to a lesser extent pDCs are critical for proliferation of naive antiviral T cells. However, other components of the primary adaptive immune response (Th1/Th2 cytokines) are essentially normal in the absence of DCs, which may account for the efficient viral clearance seen in DC-depleted mice. Thus, sufficient redundancy exists in the immune system to sustain efficient viral clearance despite loss of an APC considered essential for induction of a primary antiviral immune response.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

“…In addition, VSV disseminates to multiple organs and replicates to high titers in these mice, whereas control mice rapidly clear this virus 48 h postinfection (p.i.) (32).…”

mentioning

confidence: 99%

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Evaluation of Immunological Paradigms in a Virus Model: Are Dendritic Cells Critical for Antiviral Immunity and Viral Clearance?

Ciavarra

Stephens

Nagy

et al. 2006

The Journal of Immunology

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“…or s.c. administered therapeutic proteins should be processed by APCs in peripheral tissues and be transported to draining lymph nodes for presentation to immune effectors. Thus, the role of a specific type of APC in relation to immune response against a particular protein therapeutics remains to be surveyed in a systematic manner, as has been done in case of several pathogenic Ags (24,25). Inflammatory signals in mounting an immune response.…”

Section: Professional Apcs Are the First Immune-sensitive Depots For mentioning

confidence: 99%

Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins

Dasgupta

Bayry²,

André³

et al. 2008

The Journal of Immunology

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Alloimmunization is a crippling concern in the management of patients undergoing administration of protein therapeutics as evidenced in replacement therapy and other treatment procedures. Several issues in the genesis and modulation of such deleterious immune responses have been studied. While authors have focused on the downstream events of the specific immune response and suggested modification of protein therapeutics to eliminate epitopes that interact with B cell receptors, T cell receptors, or MHCII molecules, the mechanisms underlying Ag interaction with APCs, a step upstream of immune effectors, have been grossly neglected. We wish to emphasize that the recent knowledge in understanding the capacities of an APC to handle an Ag and the importance of the surrounding microenvironment in this process are crucial for designing novel protein therapeutics with reduced immunogenicity.

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Investigating Macrophages Plasticity Following Tumour–Immune Interactions During Oncolytic Therapies

Eftimie

2019

Acta Biotheor

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Over the last few years, oncolytic virus therapy has been recognised as a promising approach in cancer treatment, due to the potential of these viruses to induce systemic anti-tumour immunity and selectively killing tumour cells. However, the effectiveness of these viruses depends significantly on their interactions with the host immune responses, both innate (e.g., macrophages, which accumulate in high numbers inside solid tumours) and adaptive (e.g., T cells). In this article, we consider a mathematical approach to investigate the possible outcomes of the complex interactions between two extreme types of macrophages (M1 and M2 cells), effector T cells and an oncolytic Vesicular Stomatitis Virus (VSV), on the growth/elimination of B16F10 melanoma. We discuss, in terms of VSV, and macrophages levels, two different types of immune responses which could ensure tumour control and eventual elimination. We show that both innate and adaptive anti-tumour immune responses, as well as the oncolytic virus, could be very important in delaying tumour relapse and eventually eliminating the tumour. Overall this study supports the use mathematical modelling to increase our understanding of the complex immune interaction following oncolytic virotherapies. However, the complexity of the model combined with a lack of sufficient data for model parametrisation has an impact on the possibility of making quantitative predictions.

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Impact of macrophage and dendritic cell subset elimination on antiviral immunity, viral clearance and production of type 1 interferon

Cited by 43 publications

References 38 publications

Evaluation of Immunological Paradigms in a Virus Model: Are Dendritic Cells Critical for Antiviral Immunity and Viral Clearance?

Evaluation of Immunological Paradigms in a Virus Model: Are Dendritic Cells Critical for Antiviral Immunity and Viral Clearance?

Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins

Investigating Macrophages Plasticity Following Tumour–Immune Interactions During Oncolytic Therapies

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