Chitinase and Fizz family members are a generalized feature of nematode infection with selective upregulation of Ym1 and Fizz1 by antigen-presenting cells.
Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in a Brugia malayi infection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode Litomosoides sigmodontis and the gastrointestinal nematode Nippostrongylus brasiliensis. At the sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes.
Nair
Meera G
MG
Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
Gallagher
Iain J
IJ
Taylor
Matthew D
MD
Loke
P'ng
P
Coulson
Patricia S
PS
Wilson
R A
RA
Maizels
Rick M
RM
Allen
Judith E
JE
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D017178:Brugia malayi; D002688:Chitinases / Q000096:biosynthesis*; D005260:Female; D005370:Filarioidea; D036341:Intercellular Signaling Peptides and Proteins; D015847:Interleukin-4 / Q000502:physiology; D037102:Lectins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009349:Nematode Infections / Q000276:immunology*; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009559:Nippostrongylus; D011506:Proteins; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation; D001619:beta-N-Acetylhexosaminidases / Q000096:biosynthesis*
D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D011506:Proteins; C413576:Retnla protein, mouse; D015847:Interleukin-4; D020932:Nerve Growth Factor; D002688:Chitinases; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases