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. 2025 Aug;10(8):1886-1901.
doi: 10.1038/s41564-025-02051-2. Epub 2025 Jul 8.

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

Aline Sardinha-Silva  1 , Pedro H Gazzinelli-Guimaraes  2   3 , Oluwaremilekun G Ajakaye  2   4 , Fabricio M S Oliveira  3 , Tiago R Ferreira  2 , Eliza V C Alves-Ferreira  2 , Erick T Tjhin  2 , Beth Gregg  2 , Marc Y Fink  5   6 , Camila H Coelho  7   8   9 , Steven M Singer  5 , Michael E Grigg  10
Affiliations

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

Aline Sardinha-Silva et al. Nat Microbiol. 2025 Aug.

Abstract

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Adam EA, Yoder JS, Gould LH, Hlavsa MC and Gargano JW (2016). “Giardiasis outbreaks in the United States, 1971–2011.” Epidemiol Infect 144(13): 2790–2801. - PMC - PubMed
    1. Al-Mekhlafi MS, Azlin M, Nor Aini U, Shaik A, Sa’iah A, Fatmah MS, Ismail MG, Ahmad Firdaus MS, Aisah MY, Rozlida AR and Norhayati M (2005). “Giardiasis as a predictor of childhood malnutrition in Orang Asli children in Malaysia.” Trans R Soc Trop Med Hyg 99(9): 686–691. - PubMed
    1. Banik S, Renner Viveros P, Seeber F, Klotz C, Ignatius R and Aebischer T (2013). “Giardia duodenalis arginine deiminase modulates the phenotype and cytokine secretion of human dendritic cells by depletion of arginine and formation of ammonia.” Infect Immun 81(7): 2309–2317. - PMC - PubMed
    1. Barash NR, Maloney JG, Singer SM and Dawson SC (2017). “Giardia Alters Commensal Microbial Diversity throughout the Murine Gut.” Infect Immun 85(6). - PMC - PubMed
    1. Bhavnani D, Goldstick JE, Cevallos W, Trueba G and Eisenberg JN (2012). “Synergistic effects between rotavirus and coinfecting pathogens on diarrheal disease: evidence from a community-based study in northwestern Ecuador.” Am J Epidemiol 176(5): 387–395. - PMC - PubMed

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