Trefoil factor 2 negatively regulates type 1 immunity against Toxoplasma gondii

Cortez McBerry, Charlotte E. Egan, Reena Rani, Yanfen Yang, David Wu, Nicholas Boespflug, Louis Boon, Barbara Butcher, Julie Mirpuri, Simon P. Hogan, Eric Y. Denkers, Julio Aliberti, De'Broski R. Herbert

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

IL-12-mediated type 1 inflammation confers host protection against the parasitic protozoan Toxoplasma gondii. However, production of IFN-γ, another type 1 inflammatory cytokine, also drives lethality from excessive injury to the intestinal epithelium. As mechanisms that restore epithelial barrier function following infection remain poorly understood, this study investigated the role of trefoil factor 2 (TFF2), a well-established regulator of mucosal tissue repair. Paradoxically, TFF2 antagonized IL-12 release from dendritic cells (DCs) and macrophages, which protected TFF2-deficient (TFF2 -/-) mice from T. gondii pathogenesis. Dysregulated intestinal homeostasis in naive TFF2-/- mice correlated with increased IL-12/23p40 levels and enhanced T cell recruitment at baseline. Infected TFF2-/- mice displayed low rates of parasite replication and reduced gut immunopathology, whereas wild-type (WT) mice experienced disseminated infection and lethal ileitis. p38 MAPK activation and IL-12p70 production was more robust from TFF2-/-CD8+ DC compared with WT CD8 + DC and treatment of WT DC with rTFF2 suppressed TLR-induced IL-12/23p40 production. Neutralization of IFN-γ and IL-12 in TFF2 -/- animals abrogated resistance shown by enhanced parasite replication and infection-induced morbidity. Hence, TFF2 regulated intestinal barrier function and type 1 cytokine release from myeloid phagocytes, which dictated the outcome of oral T. gondii infection in mice.

Original languageEnglish (US)
Pages (from-to)3078-3084
Number of pages7
JournalJournal of Immunology
Volume189
Issue number6
DOIs
StatePublished - Sep 15 2012

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Toxoplasma
Interleukin-12
Immunity
Dendritic Cells
Ileitis
Cytokines
Parasitic Diseases
Toxoplasmosis
p38 Mitogen-Activated Protein Kinases
Intestinal Mucosa
Phagocytes
Infection
Mucous Membrane
Parasites
Homeostasis
Macrophages
Trefoil Factor-2
Inflammation
Morbidity
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

McBerry, C., Egan, C. E., Rani, R., Yang, Y., Wu, D., Boespflug, N., ... Herbert, DB. R. (2012). Trefoil factor 2 negatively regulates type 1 immunity against Toxoplasma gondii. Journal of Immunology, 189(6), 3078-3084. https://doi.org/10.4049/jimmunol.1103374

Trefoil factor 2 negatively regulates type 1 immunity against Toxoplasma gondii. / McBerry, Cortez; Egan, Charlotte E.; Rani, Reena; Yang, Yanfen; Wu, David; Boespflug, Nicholas; Boon, Louis; Butcher, Barbara; Mirpuri, Julie; Hogan, Simon P.; Denkers, Eric Y.; Aliberti, Julio; Herbert, De'Broski R.

In: Journal of Immunology, Vol. 189, No. 6, 15.09.2012, p. 3078-3084.

Research output: Contribution to journalArticle

McBerry, C, Egan, CE, Rani, R, Yang, Y, Wu, D, Boespflug, N, Boon, L, Butcher, B, Mirpuri, J, Hogan, SP, Denkers, EY, Aliberti, J & Herbert, DBR 2012, 'Trefoil factor 2 negatively regulates type 1 immunity against Toxoplasma gondii', Journal of Immunology, vol. 189, no. 6, pp. 3078-3084. https://doi.org/10.4049/jimmunol.1103374
McBerry C, Egan CE, Rani R, Yang Y, Wu D, Boespflug N et al. Trefoil factor 2 negatively regulates type 1 immunity against Toxoplasma gondii. Journal of Immunology. 2012 Sep 15;189(6):3078-3084. https://doi.org/10.4049/jimmunol.1103374
McBerry, Cortez ; Egan, Charlotte E. ; Rani, Reena ; Yang, Yanfen ; Wu, David ; Boespflug, Nicholas ; Boon, Louis ; Butcher, Barbara ; Mirpuri, Julie ; Hogan, Simon P. ; Denkers, Eric Y. ; Aliberti, Julio ; Herbert, De'Broski R. / Trefoil factor 2 negatively regulates type 1 immunity against Toxoplasma gondii. In: Journal of Immunology. 2012 ; Vol. 189, No. 6. pp. 3078-3084.
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