Giardia Duodenalis Infection Reduces Granulocyte Infiltration in an in Vivo Model of Bacterial Toxin-Induced Colitis and Attenuates Inflammation in Human Intestinal Tissue

PLoS One. 2014 Oct 7;9(10):e109087. doi: 10.1371/journal.pone.0109087. eCollection 2014.

Abstract

Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain Giardia infections may attenuate PMN accumulation by decreasing the expression of the mediators responsible for their recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / adverse effects*
  • Biopsy
  • Colitis / etiology*
  • Colitis / pathology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enterotoxins / adverse effects
  • Giardia / immunology*
  • Giardiasis / immunology*
  • Giardiasis / parasitology
  • Granulocytes / immunology*
  • Granulocytes / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / parasitology
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Neutrophils / immunology
  • Neutrophils / metabolism

Substances

  • Bacterial Toxins
  • Cytokines
  • Enterotoxins
  • Inflammation Mediators

Grant support

JA Cotton is a recipient of NSERC Alexander Graham Bell Scholarship graduate student scholarship and a joint IBD studentship from Alberta Innovates Health Solutions (AIHS) and the Crohn’s and colitis foundation of Canada (CCFC). Research in AG Buret's lab is funded by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) RT 690446, and the CCFC 10000008. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.