The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.
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.
Department of Pathology and Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
Weldy V
WV
Bonilla
Anja
A
Fröhlich
Karin
K
Senn
Sandra
S
Kallert
Marylise
M
Fernandez
Susan
S
Johnson
Mario
M
Kreutzfeldt
Ahmed N
AN
Hegazy
Christina
C
Schrick
Padraic G
PG
Fallon
Roman
R
Klemenz
Susumu
S
Nakae
Heiko
H
Adler
Doron
D
Merkler
Max
M
Löhning
Daniel D
DD
Pinschewer
D019264:Adoptive Transfer; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D006566:Herpesviridae Infections / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009336:Necrosis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology; D018144:Rhadinovirus / Q000276:immunology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014412:Tumor Virus Infections / Q000276:immunology; D015854:Up-Regulation; D014616:Vaccinia virus / Q000276:immunology; D014779:Virus Replication
C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D011994:Recombinant Proteins