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

Authors

• Aline Sardinha-Silva, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. aline.sardinhadasilva@nih.gov.
• Pedro H. Gazzinelli-Guimaraes, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Oluwaremilekun G. Ajakaye, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Fabricio M. Oliveira, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
• Tiago R. Ferreira, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Eliza V. Alves-Ferreira, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Erick T. Tjhin, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Beth Gregg, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Marc Y. Fink, Department of Biology, Georgetown University, Washington, DC, USA.
• Camila H. Coelho, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• Steven M. Singer, Department of Biology, Georgetown University, Washington, DC, USA.
• Michael E. Grigg, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. griggm@niaid.nih.gov.

Document Type

Journal Article

Publication Date

8-1-2025

Journal

Nature microbiology

Volume

10

Issue

8

DOI

10.1038/s41564-025-02051-2

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.

APA Citation

Sardinha-Silva, Aline; Gazzinelli-Guimaraes, Pedro H.; Ajakaye, Oluwaremilekun G.; Oliveira, Fabricio M.; Ferreira, Tiago R.; Alves-Ferreira, Eliza V.; Tjhin, Erick T.; Gregg, Beth; Fink, Marc Y.; Coelho, Camila H.; Singer, Steven M.; and Grigg, Michael E., "Giardia-induced Type 2 mucosal immunity attenuates intestinal inflammation caused by co-infection or colitis in mice" (2025). GW Authored Works. Paper 7525.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7525

Department

Microbiology, Immunology, and Tropical Medicine