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Macrophage-mediated enterocyte damage in BALB/c mice infected with different strains of Giardia lamblia
R Goyal1, R C Mahajan, N K Ganguly
1Dept. of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
The mechanism of mucosal injury in Giardia lamblia-infected animals and humans is not well understood, although the role of gut macrophages in killing the trophozoites is well known. It is speculated, however, that macrophage products have a role in tissue injury and inflammatory response during infection, as in other inflammatory diseases. Therefore, in the present study an attempt was made to examine the mechanism involved in enterocyte damage during giardiasis. This was achieved using co-culture of enterocytes and gut macrophages obtained from infected BALB/c mice. The extent of tissue damage was assessed by measuring the marker enzyme of enterocyte damage, lactate dehydrogenase. To investigate the role of the various proteases and free oxygen radicals released by activated macrophages on enterocyte damage, inhibitors of various proteases and free oxygen radicals were used. Superoxide radical and certain proteases were found to have important roles in bringing about enterocyte damage during this infection in mice. Parasite load, lactate dehydrogenase release, and extent of lipid peroxidation were more pronounced in mice infected with symptomatic strains than in asymptomatic ones. The theory of inflammatory cell-mediated enterocyte damage in Giardia lamblia infection is proposed.
Insights
Gut macrophages and their products, specifically superoxide radicals and proteases, contribute to enterocyte damage during Giardia lamblia infections. Symptomatic strains cause more severe damage and inflammation.
Area of Science:
- Immunology
- Gastroenterology
- Parasitology
Background:
- The precise mechanism of mucosal injury in Giardia lamblia infections remains unclear.
- Gut macrophages are known to combat Giardia trophozoites, but their role in tissue damage is speculated.
- Inflammatory responses mediated by macrophage products are implicated in various diseases.
Purpose of the Study:
- To investigate the mechanisms underlying enterocyte damage during Giardia lamblia infection.
- To determine the specific roles of macrophage-derived factors in causing tissue injury.
Main Methods:
- Co-culture of enterocytes and macrophages from Giardia-infected BALB/c mice.
- Assessment of enterocyte damage using lactate dehydrogenase (LDH) release.
- Utilizing protease and free oxygen radical inhibitors to identify damaging agents.
Main Results:
- Superoxide radicals and certain proteases released by activated macrophages play significant roles in enterocyte damage.
- Symptomatic Giardia strains induced higher parasite loads, LDH release, and lipid peroxidation compared to asymptomatic strains.
- Evidence supports an inflammatory cell-mediated mechanism of enterocyte damage.
Conclusions:
- Activated macrophages contribute to mucosal injury in giardiasis through the release of superoxide radicals and proteases.
- The severity of Giardia infection and associated enterocyte damage correlates with the strain's symptomatic nature.
- A theory of inflammatory cell-mediated enterocyte damage in Giardia lamblia infection is proposed.