Interleukin-1R Signaling Is Essential for Induction of Proapoptotic CD8 T Cells, Viral Clearance, and Pathology during Lymphocytic Choriomeningitis Virus Infection in Mice

Joeckel, Lars T.; Wallich, Reinhard; Metkar, Sunil S.; Froelich, Christopher J.; Simon, Markus M.; Borner, Christoph

doi:10.1128/jvi.00682-12

Cited by 20 publications

(22 citation statements)

References 43 publications

(73 reference statements)

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“…For example, IL-1R1−/− mice were more susceptible to respiratory influenza virus infection (influenza virus strain PR8) and showed both a markedly reduced IgM response and impaired recruitment of CD4 + T cells to the site of infection (4). IL-1R1−/− mice infected with lymphocytic choriomeningitis virus (LCMV) also exhibited reduced expansion and proliferation of virus-specific CD8 + T cells and an inability to clear LCMV compared to WT control mice (31). …”

Section: Discussionmentioning

confidence: 99%

IL-1R Type 1–Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection

Tian

Jin

Dubin

et al. 2017

The Journal of Immunology

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The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1 receptor type 1 knockout mice (IL-1R1−/−) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than wild-type (WT) mice. The phenotype of infected IL-1R1−/− mice was similar to eczema vaccinatum (EV), a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis (AD). Interestingly, the impaired cutaneous response of IL-1R1−/− mice did not reflect a systemic immune deficiency, since immunized IL-1R1−/− mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of WT mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1−/− mice contained significantly more macrophages and monocyte-derived dendritic cells (mo-DC) in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1−/− mice. These results suggest new therapeutic strategies for treatment of EV and inform assessment of risks in patients receiving IL-1 blocking antibodies for treatment of chronic inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

IL-1R Type 1–Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection

Tian

Jin

Dubin

et al. 2017

The Journal of Immunology

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“…Besides granzyme A and granzyme B, only GzmK is expressed in WT-derived CTL cells (Figure 5a), as we have previously reported. 16,27 Overall, no induction or perturbation in the expression of other granzymes was detected in Gzmk − / − CTL, suggesting that absence of GzmK is not balanced by alterations in production of other granzymes.…”

Section: Absence Of Gzmk Does Not Affect Expression Of Other Granzymementioning

confidence: 94%

Granzyme K‐deficient mice show no evidence of impaired antiviral immunity

et al. 2017

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The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin-mediated cell death in vitro, but is also reported to be non-cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease, we have deleted the granzyme K gene in mice (mutant allele: Gzmk; MGI:5636646). Gzmk mice are healthy, anatomically normal, fecund and show normal hematopoietic development. Gzmk mice readily recover from lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection. Ex vivo, virus-specific granzyme K-deficient CTL are indistinguishable from those of wild-type mice in apoptosis induction of target cells. These data suggest that granzyme K does not play an essential role in viral immunity or cytotoxicity. Our granzyme K knockout line completes the collection of mouse models for the human granzymes, and will further our understanding of their biological roles and relationships.

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“…(Joeckel et al, 2012)) and tumors (Ghiringhelli et al, 2009). Using the OT-1 model, it has recently reported that IL-1β results in increased numbers and effector function of antigen-specific T cells.…”

Section: Orchestration Of Innate and Adaptive Immunocompetent Cellsmentioning

confidence: 99%

The Interleukin-1 Family: Back to the Future

2013

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Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes 7 ligands with agonist activity (IL-1α and β, IL-18, IL-33, IL-36α, β, γ), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38) and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include 6 receptor chains forming 4 signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP) and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.

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Interleukin-1R Signaling Is Essential for Induction of Proapoptotic CD8 T Cells, Viral Clearance, and Pathology during Lymphocytic Choriomeningitis Virus Infection in Mice

Cited by 20 publications

References 43 publications

IL-1R Type 1–Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection

IL-1R Type 1–Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection

Granzyme K‐deficient mice show no evidence of impaired antiviral immunity

The Interleukin-1 Family: Back to the Future

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