Inflammatory dendritic cells--not basophils--are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen.
It is unclear how Th2 immunity is induced in response to allergens like house dust mite (HDM). Here, we show that HDM inhalation leads to the TLR4/MyD88-dependent recruitment of IL-4 competent basophils and eosinophils, and of inflammatory DCs to the draining mediastinal nodes. Depletion of basophils only partially reduced Th2 immunity, and depletion of eosinophils had no effect on the Th2 response. Basophils did not take up inhaled antigen, present it to T cells, or express antigen presentation machinery, whereas a population of FceRI(+) DCs readily did. Inflammatory DCs were necessary and sufficient for induction of Th2 immunity and features of asthma, whereas basophils were not required. We favor a model whereby DCs initiate and basophils amplify Th2 immunity to HDM allergen.
Hammad
Hamida
H
Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, University of Ghent, 9000 Ghent, Belgium. hamida.hammad@ugent.be
Plantinga
Maud
M
Deswarte
Kim
K
Pouliot
Philippe
P
Willart
Monique A M
MA
Kool
Mirjam
M
Muskens
Femke
F
Lambrecht
Bart N
BN
D000818:Animals; D017951:Antigen Presentation; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000209:etiology / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D007113:Immunity, Innate; D001239:Inhalation; D015847:Interleukin-4 / Q000276:immunology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D015847:Interleukin-4
Nature. 2009 Jan 29;457(7229):585-8
19060881
J Exp Med. 2002 Dec 16;196(12):1645-51
12486107
Nat Immunol. 2007 Nov;8(11):1217-26
17922015
Immunity. 2001 Aug;15(2):303-11
11520464
Immunity. 2008 Nov 14;29(5):795-806
18951047
J Allergy Clin Immunol. 2009 Mar;123(3):612-8
19178937
Nat Immunol. 2008 Mar;9(3):310-8
18300366
J Exp Med. 1988 Jan 1;167(1):175-82
3335830
J Exp Med. 2004 Aug 16;200(4):507-17
15314076
Int Immunol. 2008 Sep;20(9):1201-9
18632726
Blood. 2007 Aug 1;110(3):913-20
17409268
Immunity. 2005 Oct;23(4):419-29
16226507
Cell. 2008 Apr 18;133(2):235-49
18423196
J Exp Med. 2004 Jul 5;200(1):89-98
15238608
J Immunol. 2009 Jan 15;182(2):1119-28
19124755
J Immunol. 2004 Aug 15;173(4):2419-27
15294955
Nat Med. 2008 May;14(5):565-73
18454155
Nature. 1998 Mar 19;392(6673):245-52
9521319
Science. 2004 Sep 17;305(5691):1776-9
15375268
J Exp Med. 2008 Apr 14;205(4):869-82
18362170
Nat Rev Immunol. 2010 Apr;10(4):225-35
20336151
Immunity. 2002 Aug;17(2):211-20
12196292
J Immunol. 2002 Jan 15;168(2):537-40
11777943
Nat Med. 2009 Apr;15(4):410-6
19330007
J Immunol. 1996 Jul 15;157(2):607-16
8752908
Blood. 2001 Aug 15;98(4):1135-41
11493462
Nature. 1993 Mar 18;362(6417):245-8
8384701
Immunity. 2004 Mar;20(3):267-77
15030771
Science. 1990 Dec 21;250(4988):1720-3
2125367
Am J Respir Crit Care Med. 2009 May 15;179(10):883-93
19246719
J Immunol. 2001 Jan 15;166(2):1261-71
11145709
J Exp Med. 1990 Sep 1;172(3):921-9
2117636
J Exp Med. 2008 Nov 24;205(12):2839-50
18981237
Am J Respir Cell Mol Biol. 2006 Apr;34(4):426-33
16339999
J Exp Med. 2006 Jun 12;203(6):1435-46
16702603
Nat Immunol. 2009 Jul;10(7):706-12
19465908
J Immunol. 2007 Dec 1;179(11):7577-84
18025203
Immunity. 1995 Sep;3(3):259-62
7552991
J Immunol. 1998 Apr 15;160(8):4090-7
9558120
J Immunol. 1998 Sep 15;161(6):2731-9
9743330
Immunity. 2009 Sep 18;31(3):425-37
19766085
Nat Rev Immunol. 2008 Mar;8(3):193-204
18301423
J Exp Med. 2005 Mar 21;201(6):981-91
15781587
J Clin Invest. 2000 Aug;106(4):551-9
10953030
J Immunol. 2005 Jun 1;174(11):6592-7
15905497
J Exp Med. 1995 Nov 1;182(5):1591-6
7595230
Cell. 1997 May 16;89(4):587-96
9160750
J Invest Dermatol. 2003 Aug;121(2):280-8
12880419
Nat Immunol. 2010 Jul;11(7):608-17
20495560
J Clin Invest. 2005 Feb;115(2):459-67
15650773
J Leukoc Biol. 2009 Jan;85(1):64-70
18923103
Nat Rev Immunol. 2007 Jan;7(1):19-30
17170756
Nat Immunol. 2008 Jul;9(7):733-42
18516038
Immunity. 2009 Sep 18;31(3):412-24
19766084
J Immunol. 2009 Sep 15;183(6):3591-7
19684081
Nat Immunol. 2009 Jul;10(7):713-20
19465907
J Immunol. 2002 Jun 15;168(12):6199-207
12055233
J Exp Med. 1994 Feb 1;179(2):681-94
8294875
J Allergy Clin Immunol. 2001 Jun;107(6):945-57
11398070
J Exp Med. 1998 Dec 7;188(11):2019-31
9841916
Nat Immunol. 2009 Jul;10(7):697-705
19465906
J Immunol. 2010 Feb 1;184(3):1143-7
20038645
J Exp Med. 2001 Jan 1;193(1):51-60
11136820
J Exp Med. 2007 Oct 29;204(11):2759-69
17954569
J Exp Med. 1992 Oct 1;176(4):1091-8
1328464
J Clin Invest. 2000 Apr;105(7):945-53
10749574
Proc Natl Acad Sci U S A. 1990 Feb;87(4):1421-5
2106135
Nature. 1998 Mar 5;392(6671):90-3
9510253