Mucosal defences against Giardia

Abstract

Giardia lamblia (syn. G. duodenalis or G. intestinalis), the causative agent of giardiasis, is one of the most common causes worldwide of intestinal infections in humans. Symptomatic infection is characterized by diarrhoea, epigastric pain, nausea, vomiting, and weight loss, yet many infections are asymptomatic. The protozoan, unicellular parasite resides in the lumen and attaches to the epithelium and overlying mucus layers but does not invade the mucosa and causes little or no mucosal inflammation. Giardiasis is normally transient, indicating the existence of effective host defences, although re-infections can occur, which may be related to differences in infecting parasites and/or incomplete immune protection. Mucosal defences against Giardia must act in the small intestinal lumen in the absence of induction by classical inflammatory mediators. Secretory IgA antibodies have a central role in anti-giardial defence. B cell-independent mechanisms also exist and can contribute to eradication of the parasite, although their identity and physiological importance are poorly understood currently. Possible candidates are nitric oxide, antimicrobial peptides such as Paneth cell alpha-defensins, and lactoferrin. Elucidation of the key anti-giardial effector mechanisms will be important for selecting the best adjuvants in the rational development of vaccination strategies against Giardia.

Intestinal parasites: Associations with intestinal and systemic inflammation

“…On the other hand, pathogenic protozoa have shown to cause intestinal inflammation and tissue damage,17, 18 which have shown to exacerbate the systemic inflammatory process 19…”

Resistance to reinfection in mice as a vaccine model for giardiasis

“…1 We therefore measured anti-parasite IgA levels in intestinal fluid obtained from animals after euthanasia. Figure 1C indicates that high levels of IgA were found in mice given both primary and challenge infections with Giardia, as well as in mice that only received the primary infection.…”

“…G. lamblia, G. intestinalis) affects hundreds of millions of people in both the developed and developing worlds (reviewed in refs. [1][2][3]. Infections result in a range of outcomes including severe diarrhea, nutrient malabsorption, cognitive and developmental defects as well as sub-clinical infections.…”

The effects of nitric oxide on the immune response during giardiasis

“…However, it is not yet clear what immune mechanisms are responsible for effective control of infections. 50,51 Therefore, further investigation into the pathophysiology of giardiasis is needed as no pathogenic mechanisms have yet been identifi ed. Based on this consideration, the following sections focus on the importance of specifi c host effector mechanisms against Giardia.…”

“…75 The infections are normally self-limiting, as immunocompetent hosts can control and typically eradicate G. lamblia, a process that involves T and B-cells. 50,51,76,77 Several studies suggest an important role for B-cells in clearing Giardia infection. For example, infections of humans with G. lamblia result in the production of antigiardial antibodies of the IgA, IgM and IgG isotypes in mucosal secretions and serum.…”