Abstract
Our understanding of polymicrobial gastrointestinal infections and their effects on host biology remains incompletely understood. Giardia duodenalis is an ubiquitous intestinal protozoan parasite infecting animals and humans. Concomitant infections with Giardia and other gastrointestinal pathogens commonly occur. In countries with poor sanitation, Giardia infection has been associated with decreased incidence of diarrheal disease and fever, and reduced serum inflammatory markers release, via mechanisms that remain obscure. This study analyzed Giardia spp. co-infections with attaching and effacing (A/E) pathogens, and assessed whether and how the presence of Giardia modulates host responses to A/E enteropathogens, and alters intestinal disease outcome. In mice infected with the A/E pathogen Citrobacter rodentium, co-infection with Giardia muris significantly attenuated weight loss, macro- and microscopic signs of colitis, bacterial colonization and translocation, while concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse β-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G. duodenalis trophozoites and enteropathogenic Escherichia coli (EPEC) enhanced the production of the AMPs human β-defensin 2 (HBD-2) and TFF3; this effect was inhibited with treatment of G. duodenalis with cysteine protease inhibitors. Collectively, these results suggest that Giardia infections are capable of reducing enteropathogen-induced colitis while increasing production of host AMPs. Additional studies also demonstrated that Giardia was able to directly inhibit the growth of pathogenic bacteria. These results reveal novel mechanisms whereby Giardia may protect against gastrointestinal disease induced by a co-infecting A/E enteropathogen. Our findings shed new light on how microbial-microbial interactions in the gut may protect a host during concomitant infections.
Highlights
The murine enteropathogen C. rodentium is commonly used a model for enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) infections [57, 58]
Animals infected with C. rodentium lost weight from the first day of infection and did not return to baseline weight (Fig 1A), while animals co-infected with G. muris and C. rodentium lost weight at the beginning of infection but dramatically recovered weight gain by day 7 compared to mice infected with C. rodentium alone (Fig 1A)
In co-infected animals, disease activity index (DAI) scores were higher than in control animals (Fig 1B), but significantly lower than in animals infected with C. rodentium alone (Fig 1B)
Summary
G. lamblia, G. intestinalis) is a ubiquitous intestinal protozoan parasite that infects a wide array of hosts, and is responsible for diarrheal disease as well as numerous post-infectious extraintestinal pathologies [1,2,3,4,5]. It is one of the most common fecal-oral parasitic infection of the human small intestine worldwide [1, 4, 5]. In spite of high parasite loads that can exceed 106 trophozoites per centimeter of gut during the acute stage of the infection, the intestinal mucosa of Giardia-infected hosts is devoid of overt signs of inflammation [4, 13,14,15]
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