title: γδ T cells play a protective role during infection with Nippostrongylus brasiliensis by promoting goblet cell function in the small intestine.
abstract: The intestinal epithelium is rich in γδ T cells and the gut is a site of residence for a wide variety of pathogens, including nematodes. Although CD4+ T-cell receptor (TCR) -αβ+ T helper type 2 T cells are essential for the expulsion of intestinal nematodes, little information is available on the function of γδ T cells in this type of infection. Here, we demonstrate two major functions of γδ T cells as a potently protective T-cell population against Nippostrongylus brasiliensis infection using γδ T-cell-deficient (TCR-δ(-/-) ) mice. First, γδ T cells are required to initiate rapid expulsion of adult worms from the intestine and to limit egg production. Second, γδ T cells prevent the pathological intestinal damage associated with nematode infection, evident by increased clinical disease and more severe microscopic lesions in infected TCR-δ(-/-) mice. γδ T-cell deficiency led to delayed goblet cell hyperplasia in association with reduced expression of phosphorylated STAT6, MUC2, Trefoil factor-3 (TFF3) and T helper type 2 cytokines including interleukin-13 (IL-13). TCR-δ(-/-) mice also produced more interferon-γ than wild-type mice. Within the intraepithelial lymphocyte compartment, γδ T cells produced IL-13. Adoptive transfer of γδ T cells or administration of recombinant IL-13 to TCR-δ(-/-) mice successfully reduced the egg production by N. brasiliensis. Collectively, these data provide strong evidence that γδ T cells play an important role in controlling infection with intestinal nematodes and limiting infection-induced pathology.
authors: Parasitic Disease Unit, Department of Infectious Disease, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. kyoinagaki@ri.ncgm.go.jp
authors: Kyoko
authors: K
authors: Inagaki-Ohara
authors: Yukiko
authors: Y
authors: Sakamoto
authors: Taeko
authors: T
authors: Dohi
authors: Adrian L
authors: AL
authors: Smith
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D020397:Goblet Cells / Q000276:immunology* / Q000473:pathology; D018928:Immunity, Mucosal; D018793:Interleukin-13 / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D051379:Mice; D055262:Mucin-2 / Q000276:immunology; D009077:Mucins / Q000276:immunology; D009559:Nippostrongylus / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D000071165:Trefoil Factor-3
chemical_list: D018793:Interleukin-13; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3