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