Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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 basophils1. Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages2. Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-β-d-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects3. 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, AMCase4, or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B4, 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Chitin induces accumulation of innate effector cells.
Figure 2: AMCase prevents chitin-induced eosinophil and basophil recruitment.
Figure 3: Chitin-induced eosinophil recruitment is independent of Stat6 and Rag, but is dependent on BLT1.
Figure 4: Chitin induces alternatively activated macrophages.

Similar content being viewed by others


  1. Ramalingam, T. R., Reiman, R. M. & Wynn, T. A. Exploiting worm and allergy models to understand Th2 cytokine biology. Curr. Opin. Allergy Clin. Immunol. 5, 392–398 (2005)

    Article  CAS  Google Scholar 

  2. Gordon, S. Alternative activation of macrophages. Nature Rev. Immunol. 3, 23–35 (2003)

    Article  CAS  Google Scholar 

  3. Bowman, S. M. & Free, S. J. The structure and synthesis of the fungal cell wall. Bioessays 28, 799–808 (2006)

    Article  Google Scholar 

  4. Zhu, Z. et al. Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science 304, 1678–1682 (2004)

    Article  ADS  CAS  Google Scholar 

  5. Nair, M. G., Guild, K. J. & Artis, D. Novel effector molecules in type 2 inflammation: lessons drawn from helminth infection and allergy. J. Immunol. 177, 1393–1399 (2006)

    Article  CAS  Google Scholar 

  6. Finkelman, F. D. et al. Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol. Rev. 201, 139–155 (2004)

    Article  CAS  Google Scholar 

  7. Zhang, Y., Foster, J. M., Nelson, L. S., Ma, D. & Carlow, C. K. The chitin synthase genes chs-1 and chs-2 are essential for C. elegans development and responsible for chitin deposition in the eggshell and pharynx, respectively. Dev. Biol. 285, 330–339 (2005)

    Article  CAS  Google Scholar 

  8. Mohrs, M., Shinkai, K., Mohrs, K. & Locksley, R. M. Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter. Immunity 15, 303–311 (2001)

    Article  CAS  Google Scholar 

  9. Boot, R. G. et al. Identification of a novel acidic mammalian chitinase distinct from chitotriosidase. J. Biol. Chem. 276, 6770–6778 (2001)

    Article  CAS  Google Scholar 

  10. Boot, R. G., Renkema, G. H., Strijland, A., van Zonneveld, A. J. & Aerts, J. M. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J. Biol. Chem. 270, 26252–26256 (1995)

    Article  CAS  Google Scholar 

  11. Jin, H. M. et al. Genetic characterization of the murine Ym1 gene and identification of a cluster of highly homologous genes. Genomics 54, 316–322 (1998)

    Article  CAS  Google Scholar 

  12. Huang, W. W. et al. Molecular and biological characterization of the murine leukotriene B4 receptor expressed on eosinophils. J. Exp. Med. 188, 1063–1074 (1998)

    Article  CAS  Google Scholar 

  13. Usami, Y., Okamoto, Y., Takayama, T., Shigemasa, Y. & Minami, S. Chitin and chitosan stimulate canine polymorphonuclear cells to release leukotriene B4 and prostaglandin E2. J. Biomed. Mater. Res. 42, 517–522 (1998)

    Article  CAS  Google Scholar 

  14. Tager, A. M. et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nature Immunol. 4, 982–990 (2003)

    Article  CAS  Google Scholar 

  15. Wolters, P. J. et al. Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient KitW-sh/KitW-sh sash mice. Clin. Exp. Allergy 35, 82–88 (2005)

    Article  CAS  Google Scholar 

  16. Machado, E. R. et al. Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis. J. Immunol. 175, 3892–3899 (2005)

    Article  CAS  Google Scholar 

  17. Phillips, C., Coward, W. R., Pritchard, D. I. & Hewitt, C. R. Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites. J. Leukoc. Biol. 73, 165–171 (2003)

    Article  CAS  Google Scholar 

  18. Shibata, Y., Foster, L. A., Bradfield, J. F. & Myrvik, Q. N. Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse. J. Immunol. 164, 1314–1321 (2000)

    Article  CAS  Google Scholar 

  19. Keyhani, N. O. & Roseman, S. Physiological aspects of chitin catabolism in marine bacteria. Biochim. Biophys. Acta 1473, 108–122 (1999)

    Article  CAS  Google Scholar 

  20. Merzendorfer, H. & Zimoch, L. Chitin metabolism in insects: structure, function and regulation of chitin synthases and chitinases. J. Exp. Biol. 206, 4393–4412 (2003)

    Article  CAS  Google Scholar 

  21. Kaku, H. et al. Plant cells recognize chitin fragments for defense signaling through a plasma membrane receptor. Proc. Natl Acad. Sci. USA 103, 11086–11091 (2006)

    Article  ADS  CAS  Google Scholar 

  22. Hernandez Prada, J. A. et al. Ancient evolutionary origin of diversified variable regions demonstrated by crystal structures of an immune-type receptor in amphioxus. Nature Immunol. 7, 875–882 (2006)

    Article  Google Scholar 

  23. Voehringer, D., Reese, T. A., Huang, X., Shinkai, K. & Locksley, R. M. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J. Exp. Med. 203, 1435–1446 (2006)

    Article  CAS  Google Scholar 

  24. Cartier, A. et al. Prevalence of crab asthma in crab plant workers in Newfoundland and Labrador. Int. J. Circumpolar Health 63, (Suppl. 2)333–336 (2004)

    Article  ADS  Google Scholar 

  25. Adachi, O. et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9, 143–150 (1998)

    Article  CAS  Google Scholar 

  26. Tager, A. M. et al. BLTR mediates leukotriene B4-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis. J. Exp. Med. 192, 439–446 (2000)

    Article  CAS  Google Scholar 

  27. Voehringer, D., Shinkai, K. & Locksley, R. M. Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 20, 267–277 (2004)

    Article  CAS  Google Scholar 

  28. Reinhardt, R. L., Hong, S., Kang, S. J., Wang, Z. E. & Locksley, R. M. Visualization of IL-12/23p40 in vivo reveals immunostimulatory dendritic cell migrants that promote Th1 differentiation. J. Immunol. 177, 1618–1627 (2006)

    Article  CAS  Google Scholar 

  29. Van Rooijen, N. & Sanders, A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J. Immunol. Methods 174, 83–93 (1994)

    Article  CAS  Google Scholar 

  30. Zhang, J. Q., Biedermann, B., Nitschke, L. & Crocker, P. R. The murine inhibitory receptor mSiglec-E is expressed broadly on cells of the innate immune system whereas mSiglec-F is restricted to eosinophils. Eur. J. Immunol. 34, 1175–1184 (2004)

    Article  CAS  Google Scholar 

  31. Glasser, S. W. et al. Genetic element from human surfactant protein SP-C gene confers bronchiolar-alveolar cell specificity in transgenic mice. Am. J. Physiol. 261, L349–L356 (1991)

    ADS  CAS  PubMed  Google Scholar 

Download references


We thank D. Stetson for assistance with recombinant protein production, G. Caughey, X. Xu and S. Akira for mice and reagents, N. Flores, C. McArthur and L. Stowring for expert technical assistance, and A. DeFranco and J. Bluestone for discussions. This work was supported by the NIH, the HHMI and the Sandler Asthma Basic Research Centre at UCSF.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Richard M. Locksley.

Ethics declarations

Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures S1-S4 with Legends. (PDF 661 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reese, T., Liang, HE., Tager, A. et al. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature 447, 92–96 (2007).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing