Chitin induces accumulation in tissue of innate immune cells associated with allergy.
Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils. Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages. Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-beta-D-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects. Here, we show that chitin induces the accumulation in tissue of IL-4-expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase, or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B(4), which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase.
Reese
Tiffany A
TA
Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, California 94143-0795, USA.
Liang
Hong-Erh
HE
Tager
Andrew M
AM
Luster
Andrew D
AD
Van Rooijen
Nico
N
Voehringer
David
D
Locksley
Richard M
RM
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology; D002686:Chitin / Q000276:immunology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology* / Q000469:parasitology; D007113:Immunity, Innate / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D051193:Toll-Like Receptors / Q000172:deficiency / Q000235:genetics
C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D051193:Toll-Like Receptors; D002686:Chitin