Transcript Efficient Immunization by Targeting Human DC

Nuocytes represent a new innate effector leukocyte
that mediates type-2 immunity
Daniel R. Neill1*, See Heng Wong1*, Agustin Bellosi1*, Robin J. Flynn1, Maria Daly1, Theresa K. A. Langford1,
Christine Bucks2, Colleen M. Kane2, Padraic G. Fallon3, Richard Pannell1, Helen E. Jolin1 & Andrew N. J. McKenzie1
ZIB Paper presentation
07.02.2011
Wiebke Ginter
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Type II immunity and Question
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Plays role in helminth infection and asthma
Eosinophilia, mucus secretion, IgE production
IL-4, IL5, IL-13
Produced by basophils, eosinophils and mast cells
Role in Nippostrongylus brasiliensis expulsion unknown
Nippostrongylus brasiliensis
• intestinal nematode of rodents
• closely related to the human hookworms (Ancylostoma and
Necator)
• infect 740 million people in tropical countries
• N. brasiliensis widely used model for nematode parasites
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Maizels, 2003, Nat. Rev. Immunol
Type II immunity and Question
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Plays role in helminth infection and asthma
Eosinophilia, mucus secretion, IgE production
IL-4, IL5, IL-13
Produced by basophils, eosinophils and mast cells
Role in Nippostrongylus brasiliensis expulsion unknown
IL-13 is critical in immune response to helminths and asthma
Which cell types to produce this cytokine?
Supp. 1a
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CD4+ splenocytes
Th1 conditions
Th2 conditions
Supp.1
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Localisation of eGFP+ cells
Fig. 1c
Supp. 2b
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Surface markers
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Supp. 2a,c
New cells are no mast, B, T, NK or LTi cells
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Induction of Nuocytes by IL-25 and IL-33
Nuocytes: Lin- eGFP+T1/ST2+IL17BR+
Fig. 1
IL-25 receptor
SU of IL-33 receptor
 Direct action of these IL
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 Redundant action
Presence in imunosurveillance sites
Supp. 4
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Helminth infection
Small intestine
Supp. 2d
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Fig. 2a
IL25 and IL33: partially redundant roles
Fig.2
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Il17br-/-
Il1rl1-/-
IL17br-/-Il1rl1-/-
No IL25R
No SU IL33R
No IL25R, IL33R
Nuocyte Cultures
Fig. 3
 IL33 and IL7 needed for expansion
 Most cell surface markers maintained
 Did not differentiate
Supp. 8
Nuocytes: Lin- ICOS+T1/ST2+IL17BR+IL-7Rα+
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Cytokine profile
Fig. 3
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Supp. 9
Adoptive transfer of cultured nuocytes into Il17br-/- mice restores an IL25responsive phenotype
Il17br-/-
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Restoring protective IR in IL17BR-/- mice
Fig. 4
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IL13 of nuocytes is necessary and sufficient for worm expulsion
IL13 from nuocytes is the only important source
Fig. 4
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Dialogue between T cells and nuocytes
Enhance cytokines, augment resp
T cells
Nuocytes
Maintain: expansion survival
Fig. 4
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Summary
• new class of cells: Nuocytes
• important for the type-2 immunity: protection from parasitic helminths
• release of type II cytokines, activating eosinophiles and goblet cells and
secreting mucus and IgE
• Key source of IL-13 release during early steps of helminth infection
• Expand rapidly in response to IL-25 and IL-33 (type-2 initiators)
Enhance cytokines, augment resp
• Lack: nuocytes expansion ↓, defect in worm expulsion
T cells
• present in immunosurveillance sites
• Secrete high levels of IL13 and IL5
• Enhance T cell responses
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Nuocytes
Maintain: expansion survival
Supplementary
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Saenz, 2010, Trends in Immunology
Surface markers
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Supp. 2a,c
Adoptive transfer of wild-type nuocytes, but not IL13-deficient nuocytes,
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restores rapid worm expulsion in N. brasiliensis-infected Il17br / mice.
DR
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Neill et al. Nature 000, 1-4 (2010) doi:10.1038/nature08900