The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses

Weldy V Bonilla; Anja Fröhlich; Karin Senn; Sandra Kallert; Marylise Fernandez; Susan Johnson; Mario Kreutzfeldt; Ahmed N Hegazy; Christina Schrick; Padraic G Fallon; Roman Klemenz; Susumu Nakae; Heiko Adler; Doron Merkler; Max Löhning; Daniel D Pinschewer

doi:10.1126/science.1215418

The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses

Science. 2012 Feb 24;335(6071):984-9. doi: 10.1126/science.1215418. Epub 2012 Feb 9.

Authors

Weldy V Bonilla¹, Anja Fröhlich, Karin Senn, Sandra Kallert, Marylise Fernandez, Susan Johnson, Mario Kreutzfeldt, Ahmed N Hegazy, Christina Schrick, Padraic G Fallon, Roman Klemenz, Susumu Nakae, Heiko Adler, Doron Merkler, Max Löhning, Daniel D Pinschewer

Affiliation

¹ Department of Pathology and Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.

PMID: 22323740
DOI: 10.1126/science.1215418

Abstract

Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adoptive Transfer
Animals
Arenaviridae Infections / immunology*
Arenaviridae Infections / pathology
Cell Differentiation
Gene Expression Profiling
Herpesviridae Infections / immunology*
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33
Interleukins / genetics
Interleukins / immunology
Interleukins / metabolism*
Lymphocyte Activation
Lymphocytic choriomeningitis virus / immunology*
Lymphocytic choriomeningitis virus / physiology
Mice
Mice, Transgenic
Necrosis
Receptors, Interleukin / genetics
Receptors, Interleukin / metabolism
Recombinant Proteins / immunology
Rhadinovirus / immunology*
Signal Transduction
Stromal Cells / immunology
Stromal Cells / metabolism
T-Lymphocytes, Cytotoxic / immunology*
T-Lymphocytes, Cytotoxic / transplantation
Tumor Virus Infections / immunology
Up-Regulation
Vaccinia virus / immunology
Virus Replication

Substances

Il1rl1 protein, mouse
Il33 protein, mouse
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33
Interleukins
Receptors, Interleukin
Recombinant Proteins

Associated data

GEO/GSE34392