Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103+ dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.



  1. 1.

    , & Chitin synthesis and fungal pathogenesis. Curr. Opin. Microbiol. 13, 416–423 (2010).

  2. 2.

    , & The chitin crystallite in arthropod cuticle. J. Cell Sci. 21, 73–82 (1976).

  3. 3.

    et al. Nematode chitin synthases: gene structure, expression and function in Caenorhabditis elegans and the plant parasitic nematode Meloidogyne artiellia. Mol. Genet. Genomics 266, 28–34 (2001).

  4. 4.

    , , & Parasitic nematodes have two distinct chitin synthases. Mol. Biochem. Parasitol. 142, 126–132 (2005).

  5. 5.

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

  6. 6.

    , , , & Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins. J. Biol. Chem. 270, 2198–2202 (1995).

  7. 7.

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

  8. 8.

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

  9. 9.

    , & Increased expression of acidic mammalian chitinase in chronic rhinosinusitis with nasal polyps. Am. J. Rhinol. 20, 330–335 (2006).

  10. 10.

    et al. Acidic mammalian chitinase is not a critical target for allergic airway disease. Am. J. Respir. Cell Mol. Biol. 46, 71–79 (2012).

  11. 11.

    et al. AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites. Proc. Natl. Acad. Sci. USA 112, E2891–E2899 (2015).

  12. 12.

    Type 2 cytokines: mechanisms and therapeutic strategies. Nat. Rev. Immunol. 15, 271–282 (2015).

  13. 13.

    et al. Chitinase and Fizz family members are a generalized feature of nematode infection with selective upregulation of Ym1 and Fizz1 by antigen-presenting cells. Infect. Immun. 73, 385–394 (2005).

  14. 14.

    et al. The transcription factor GATA3 is critical for the development of all IL-7Rα-expressing innate lymphoid cells. Immunity 40, 378–388 (2014).

  15. 15.

    et al. Polymorphisms and haplotypes of acid mammalian chitinase are associated with bronchial asthma. Am. J. Respir. Crit. Care Med. 172, 1505–1509 (2005).

  16. 16.

    et al. Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. PLoS Pathog. 11, e1004701 (2015).

  17. 17.

    et al. Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit. J. Allergy Clin. Immunol. 122, 944–950 (2008).

  18. 18.

    , , & Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J. Immunol. 171, 3655–3667 (2003).

  19. 19.

    et al. Controlling soil-transmitted helminthiasis in pre-school-age children through preventive chemotherapy. PLoS Negl. Trop. Dis. 2, e126 (2008).

  20. 20.

    , & Mucosal immune responses following intestinal nematode infection. Parasite Immunol. 36, 439–452 (2014).

  21. 21.

    et al. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J. Exp. Med. 206, 2947–2957 (2009).

  22. 22.

    et al. Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage. Nat. Immunol. 15, 1116–1125 (2014).

  23. 23.

    et al. Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis. Am. J. Pathol. 167, 1243–1256 (2005).

  24. 24.

    et al. Muc5ac: a critical component mediating the rejection of enteric nematodes. J. Exp. Med. 208, 893–900 (2011).

  25. 25.

    , , , & Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. J. Exp. Med. 189, 1565–1572 (1999).

  26. 26.

    et al. IL-13, IL-4Rα, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 8, 255–264 (1998).

  27. 27.

    et al. Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J. Exp. Med. 202, 1063–1073 (2005).

  28. 28.

    , , , & Insectivorous bats digest chitin in the stomach using acidic mammalian chitinase. PLoS One 8, e72770 (2013).

  29. 29.

    & Control of adaptive immunity by the innate immune system. Nat. Immunol. 16, 343–353 (2015).

  30. 30.

    et al. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205, 2139–2149 (2008).

  31. 31.

    , , , & Induction of an IgE response in mice by Nippostrongylus brasiliensis: characterization of lymphoid cells with intracytoplasmic or surface IgE. J. Immunol. 130, 350–356 (1983).

  32. 32.

    et al. B cells have distinct roles in host protection against different nematode parasites. J. Immunol. 184, 5213–5223 (2010).

Download references


This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank MedImmune for generating the anti-AMCase rabbit sera, C. Mainhart for genotyping, T. Gieseck and K. Kindrachuk for discussions, and the animal care staffs of Buildings 50 and 14BS at the US National Institutes of Health's Bethesda, Maryland campus for the conscientious care of mice.

Author information


  1. Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

    • Kevin M Vannella
    • , Thirumalai R Ramalingam
    • , Kevin M Hart
    • , Rafael de Queiroz Prado
    • , Joshua Sciurba
    • , Luke Barron
    • , Lee A Borthwick
    • , Margaret Mentink-Kane
    • , Sandra White
    • , Robert W Thompson
    • , Allen W Cheever
    •  & Thomas A Wynn
  2. Tissue Fibrosis and Repair Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

    • Lee A Borthwick
  3. United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Center, Beltsville, Maryland, USA.

    • Allen D Smith
    •  & Joseph F Urban Jr
  4. Infectious Disease Pathology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.

    • Kevin Bock
    •  & Ian Moore
  5. Inflammation and Immunity, Pfizer Worldwide R&D, Cambridge, Massachusetts, USA.

    • Lori J Fitz


  1. Search for Kevin M Vannella in:

  2. Search for Thirumalai R Ramalingam in:

  3. Search for Kevin M Hart in:

  4. Search for Rafael de Queiroz Prado in:

  5. Search for Joshua Sciurba in:

  6. Search for Luke Barron in:

  7. Search for Lee A Borthwick in:

  8. Search for Allen D Smith in:

  9. Search for Margaret Mentink-Kane in:

  10. Search for Sandra White in:

  11. Search for Robert W Thompson in:

  12. Search for Allen W Cheever in:

  13. Search for Kevin Bock in:

  14. Search for Ian Moore in:

  15. Search for Lori J Fitz in:

  16. Search for Joseph F Urban in:

  17. Search for Thomas A Wynn in:


K.M.V., T.R.R. and T.A.W. conceived and designed the experiments; K.M.V., A.D.S., K.M.H., L.A.B., R.W.T., S.W., J.F.U., R.d.Q.P. and J.S. performed the experiments; I.M. and K.B. performed immunofluorescence techniques; K.M.V., T.R.R., A.D.S., A.W.C., L.B., L.A.B., M.M.-K., T.A.W., J.F.U. and R.d.Q.P. analyzed the data; A.D.S., A.W.C., I.M., J.F.U. and L.J.F. contributed reagents; K.M.V., T.R.R. and T.A.W. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Thomas A Wynn.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–5

About this article

Publication history






Further reading

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