A critical role for IL-13 in resistance to intestinal nematode infection.

Mice in which either the IL-4 or the IL-13 gene has been disrupted (IL-4 KO and IL-13 KO) were susceptible to infection with the intestinal nematode Trichuris muris, whereas their wild-type littermates were highly resistant and expelled the parasite. IL-4 KO mice showed diminished Th2-type responses with T. muris infection and also failed to produce parasite-specific IgG1 Abs. Although IL-13 KO mice made reduced Th2-type responses early in infection, they were capable of generating strong Th2-type responses at later time points and were unable to regulate the magnitude of their Ab isotype response. These results confirm the importance of IL-4 in resistance to T. muris and provide the first demonstration of an important role for IL-13 in resistance to helminth infection. The IL-13 KO mouse had a separate phenotype to that of the IL-4 KO mouse, suggesting that both IL-4 and IL-13 play important yet different roles in mediating immunity to intestinal helminths.

[1]  D. Cockayne,et al.  IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia: correlation with down-modulation of TNF-alpha, IFN-gamma, and IL-12 production. , 1997, Journal of immunology.

[2]  T. Mosmann,et al.  Continuous administration of Il-13 to mice induces extramedullary hemopoiesis and monocytosis. , 1996, Journal of immunology.

[3]  A. Ohta,et al.  Involvement of IL-4-producing Vbeta8.2+ CD4+ CD62L- CD45RB- T cells in non-MHC gene-controlled predisposition toward skewing into T helper type-2 immunity in BALB/c mice. , 1997, Journal of immunology.

[4]  G. Trinchieri,et al.  Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production , 1995, The Journal of experimental medicine.

[5]  K. Rajewsky,et al.  Generation and analysis of interleukin-4 deficient mice. , 1991, Science.

[6]  R. Coffman,et al.  Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures , 1988, The Journal of experimental medicine.

[7]  K. Else,et al.  Correlations between worm burden and markers of Th1 and Th2 cell subset induction in an inbred strain of mouse infected with Trichuris muris , 1993, Parasite immunology.

[8]  Martin Bachmann,et al.  Disruption of the murine IL-4 gene blocks Th2 cytokine responses , 1993, Nature.

[9]  K. Else,et al.  Antibody-independent effector mechanisms in resistance to the intestinal nematode parasite Trichuris muris , 1996, Infection and immunity.

[10]  W. Paul,et al.  Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Wakelin Acquired immunity to Trichuris muris in the albino laboratory mouse , 1967, Parasitology.

[12]  K. Else,et al.  The effects of H-2 and non-H-2 genes on the expulsion of the nematode Trichuris muris from inbred and congenic mice , 1988, Parasitology.

[13]  J. D. de Vries,et al.  Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. , 1994, Immunology today.

[14]  F. Finkelman,et al.  Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. , 1991, Journal of immunology.

[15]  R. Coffman,et al.  Lymphokine control of in vivo immunoglobulin isotype selection. , 1990, Annual review of immunology.

[16]  R. Maizels,et al.  Nippostrongylus brasiliensis: cytokine responses and nematode expulsion in normal and IL-4-deficient mice. , 1996, Experimental parasitology.

[17]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[18]  K. Else,et al.  The influence of genes mapping within the major histocompatibility complex on resistance to Trichuris muris infections in mice , 1990, Parasitology.

[19]  J. D. de Vries,et al.  Interleukin‐13 is produced by activated human CD45RA+ and CD45R0+ T cells: modulation by interleukin‐4 and interleukin‐12 , 1996, European journal of immunology.

[20]  K. Else,et al.  Interleukin‐12 promotes a chronic intestinal nematode infection , 1997, European journal of immunology.

[21]  W. Solbach,et al.  IL-4-deficient Balb/c mice resist infection with Leishmania major , 1996, The Journal of experimental medicine.

[22]  F. Finkelman,et al.  Cytokine-mediated regulation of chronic intestinal helminth infection , 1994, The Journal of experimental medicine.

[23]  F. Podlaski,et al.  Interleukin‐12 profoundly up‐regulates the synthesis of antigen‐specific complement‐fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo , 1995, European journal of immunology.

[24]  S. Kaufmann,et al.  Effects of IL-13 on murine listeriosis. , 1997, International immunology.

[25]  K. Else,et al.  Modulation of cytokine production and response phenotypes in murine trichuriasis , 1992, Parasite immunology.

[26]  P. Casellas,et al.  lnterleukin-13 is a new human lymphokine regulating inflammatory and immune responses , 1993, Nature.

[27]  F. Finkelman,et al.  The Importance of Th2 Cytokines in Protective Immunity to Nematodes , 1992, Immunological reviews.

[28]  E. Minshall,et al.  In vivo expression of IL-12 and IL-13 in atopic dermatitis. , 1996, The Journal of allergy and clinical immunology.

[29]  F. Finkelman,et al.  Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models. , 1997, Annual review of immunology.

[30]  K. Else,et al.  Cellular immune responses to the murine nematode parasite Trichuris muris. I. Differential cytokine production during acute or chronic infection. , 1991, Immunology.

[31]  R. Grencis Th2-mediated host protective immunity to intestinal nematode infections. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[32]  M. Daly,et al.  Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  K. Else,et al.  Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. , 1992, Immunology.

[34]  Muriel T. Davisson,et al.  Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice , 1997, Nature Genetics.

[35]  R. Fernandez-Botran,et al.  Interleukin 4 mediates autocrine growth of helper T cells after antigenic stimulation. , 1986, Proceedings of the National Academy of Sciences of the United States of America.