<i>Giardia duodenalis</i> Infection Reduces Granulocyte Infiltration in an <i>In Vivo</i> Model of Bacterial Toxin-Induced Colitis and Attenuates Inflammation in Human Intestinal Tissue

<div><p><i>Giardia duodenalis (syn. G. intestinalis, G. lamblia)</i> is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although <i>Giardia</i>-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, <i>Giardia</i> infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated <i>Giardia</i> 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. <i>Giardia</i> cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting <i>Giardia</i> targets PMN accumulation. However, the ability of <i>Giardia</i> infections to attenuate PMN accumulation <i>in vivo</i> and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that <i>Giardia</i> infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of <i>Clostridium difficile</i> 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. <i>Giardia</i> trophozoite isolates that attenuated granulocyte infiltration <i>in vivo</i> 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 <i>Giardia</i> infections may attenuate PMN accumulation by decreasing the expression of the mediators responsible for their recruitment.</p>