{Reference Type}: Journal Article
{Title}: Giardia intestinalis reshapes mucosal immunity toward a Type 2 response that attenuates inflammatory bowel-like diseases.
{Author}: Sardinha-Silva A;Gazzinelli-Guimaraes PH;Ajakaye OG;Ferreira TR;Alves-Ferreira EVC;Tjhin ET;Gregg B;Fink MY;Coelho CH;Singer SM;Grigg ME;
{Journal}: bioRxiv
{Volume}: 0
{Issue}: 0
{Year}: 2024 Mar 6
暂无{DOI}: 10.1101/2024.03.02.583119
{Abstract}: Diarrheal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with Giardia intestinalis decreases the severity of diarrhea. Here, we show that Giardia is highly prevalent in the stools of asymptomatic school-aged children. It orchestrates a Th2 mucosal immune response, characterized by increased antigen-specific Th2 cells, IL-25, Type 2-associated cytokines, and goblet cell hyperplasia. Giardia infection expanded IL-10-producing Th2 and GATA3+ Treg cells that promoted chronic carriage, parasite transmission, and conferred protection against Toxoplasma gondii-induced lethal ileitis and DSS-driven colitis by downregulating proinflammatory cytokines, decreasing Th1/Th17 cell frequency, and preventing collateral tissue damage. Protection was dependent on STAT6 signaling, as Giardia-infected STAT6-/- mice no longer regulated intestinal bystander inflammation. Our findings demonstrate that Giardia infection reshapes mucosal immunity toward a Type 2 response, which confers a mutualistic protection against inflammatory disease processes and identifies a critical role for protists in regulating mucosal defenses.