Gastrointestinal helminth infections are widespread across the globe and throughout the animal kingdom where they are responsible for the loss of productivity in cattle and other livestock. They cause infections in humans too which has a considerable impact as they infect over 1 billion people worldwide. In humans there is considerable morbidity and infection is associated predominantly with four species of helminths (Ascaris lumbricoides, Acylostoma duodenale, Nector americanus and Trichuris trichiura.) Infection of humans with these parasites has considerable impact on human health with estimates of 39 million disability adjusted life years (DALYs). Current treatment largely depends on chemotherapy with anthelmintics. This is only partially effective, however, as over time parasite resistance has increased tremendously. Understanding the immune system of the host against the parasite is a better way to take control of the situation. By doing so, there can be ways to eradicate the parasite and further provide protection. Animal models have contributed considerably to this understanding.

Animal Models

Trichuris trichiura, the human whipworm infects approx over 1000 million people across the world. The mouse whipworm, Trichuris muris proves to be a useful model of study in order to understand the human whipworm as it has an immunological cross reactivity with T. trichiura. The mouse provides an easily maintained host which can be kept in controlled clean conditions and hence appropriate for study. Current research focuses on T. muris infections and the inbred strains of mice.

Trichuris Muris Life cycle

T. muris infection follows a faecal-oral route where the parasite is transmitted by ingestion of infective eggs released in faeces by the host. These eggs pass through the digestive tract and accumulate in caecum; this process stimulates hatching. The first larval stage (L1) hatched from eggs are detected in caecum as early as 90mins post infection (p.i). The larvae, then penetrates the mucosal tissues and epithelia. Larvae reside in the caecum, anchored into the epithelial layer and no penetration of basement membrane has been detected in infection. The crypt larvae grow and undergo moults at day 9, 17 and 22 p.i before reaching maturity at day 32 p.i. During this time, the larvae extend up the crypt axis and the anterior of the worm forms tunnels composed of enterocytes cells. By adulthood worms protrude into the lumen which is needed for mating and subsequent egg release into the faeces.

Immune response to Trichuris Muris

Many studies have been carried out in order to study the infections of T. muris in lab mice. I would move these references. The infection varied according to the strain of mice used. The first experiments were carried out which exhibited over 70% of the worm elimination was in Schofield mice. The 30% mice who did not expel worms were still susceptible to challenge. As the majority of the mice expelled their parasites before the worms reached maturity it was thought that immunity may be stimulated by larval stages. In order to test this, Wakelin prematurely ended infection with antihelmintic treatment at different stages of larval development. It was observed that infections abbreviated after 14 days stimulated immunity, but it was enhanced further if infection was allowed to continue until 18 days p.i. Hence it was seen that antigen was not secreted at specific larval stages and immunity increased by a longer exposure to parasite antigens.

A comparative study was done in five outbred and one inbred strain of mouse. It was seen that only the inbred strain exhibited a uniform response and suggested variation to resistance is a host genetic component. Cortisone treatment induced worm survival and this suggested a time point which is an important period for worm survival/expulsion.

Another study to understand the acquired immunity was undertaken by. The cells/serum from infected animal was passively transferred and protection in inbred NIH mouse strain was provided as they expelled their worms quickly. MLN cells (Mesenteric lymph node) conferred effective protection to infection and serum transfer was successful to a lesser extent. The thymus was also important for resistance to the parasite proving that MLN cells taken from donors at day 21 post infection were very efficient in stimulating resistance in the receipient but not if the mouse had been sub-lethally irradiated prior to transfer. Hence, it was suggested that even if the lymphoid donor cells could transfer resistance, an endogenous host was essential. Other cell populations also played an important role in T. muris infections apart from MLN.

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