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<p>Diarrhoeal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with the protozoan parasite <i>Giardia intestinalis</i> decreases diarrhoeal severity. Here we show a high incidence of asymptomatic <i>Giardia</i> infection in school-aged children from Nigeria. In a mouse model, <i>Giardia</i> induced a Type 2 mucosal immune response, characterized by antigen-specific Th2 cells, IL-25, Type 2 cytokines, and goblet cell hyperplasia. Single-cell RNA sequencing and multiparameter flow cytometry revealed expansion of IL-10-producing Th2 cells, which promoted parasite persistence and protected against <i>Toxoplasma gondii</i>-induced ileitis and dextran sulfate sodium-induced colitis. This protective effect was STAT6 dependent, as IL-4R blockade or STAT6 deficiency impaired IL-10<sup>+</sup> Th2 responses, resulting in Th1/Th17-driven tissue damage, inflammation and clearance of <i>Giardia</i> infection. Our findings demonstrate that <i>Giardia</i> reshapes mucosal immunity toward a Type 2 response, facilitating parasitism and conferring mutualistic protection from inflammatory pathologies, highlighting a key role for protists in mucosal defence regulation.</p>

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Giardia-induced Type 2 mucosal immunity attenuates intestinal inflammation caused by co-infection or colitis in mice

  • 期刊论文

  • 发表日期：

    2025年7月8日

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  • Aline Sardinha-Silva,
  • Pedro H. Gazzinelli-Guimaraes,
  • Oluwaremilekun G. Ajakaye,
  • Fabricio M. S. Oliveira,
  • Tiago R. Ferreira,
  • Eliza V. C. Alves-Ferreira,
  • Erick T. Tjhin,
  • Beth Gregg,
  • Marc Y. Fink,
  • Camila H. Coelho,
  • Steven M. Singer,
  • Michael E. Grigg

摘要

Diarrhoeal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with the protozoan parasite Giardia intestinalis decreases diarrhoeal severity. Here we show a high incidence of asymptomatic Giardia infection in school-aged children from Nigeria. In a mouse model, Giardia induced a Type 2 mucosal immune response, characterized by antigen-specific Th2 cells, IL-25, Type 2 cytokines, and goblet cell hyperplasia. Single-cell RNA sequencing and multiparameter flow cytometry revealed expansion of IL-10-producing Th2 cells, which promoted parasite persistence and protected against Toxoplasma gondii-induced ileitis and dextran sulfate sodium-induced colitis. This protective effect was STAT6 dependent, as IL-4R blockade or STAT6 deficiency impaired IL-10+ Th2 responses, resulting in Th1/Th17-driven tissue damage, inflammation and clearance of Giardia infection. Our findings demonstrate that Giardia reshapes mucosal immunity toward a Type 2 response, facilitating parasitism and conferring mutualistic protection from inflammatory pathologies, highlighting a key role for protists in mucosal defence regulation.