CYTOKINE AND CHEMOKINE RESPONSES UNDERLYING ACUTE AND CHRONIC TRICHURIS MURIS INFECTION

Abstract

Intestinal nematode parasites are some of the most prevalent infections of man. Infections tend to be chronic and, after drug treatment, have high reinfection rates. Control programs relying solely on drugs are thus at best short-term solutions; immunization programs are our long-term goal. A prerequisite to effective disease control by immunotherapy is the need to understand the immune responses that underlie resistance and susceptibility to infection. Most of our current understanding of immunity to Trichuris trichiura infection in man has come from the laboratory model, Trichuris muris in the mouse. Over the last decade we have learned that the type of T helper cell response (Th1 or Th2) mounted by the host is critical to the outcome of infection, and we have identified key Th2- and Th1- associated cytokines that contribute to resistance or susceptibility, respectively. Notably, the number of these key cytokines is still growing. Our model of immunity to Trichuris has developed from one revolving round IL-4 and IFN-γ to one that also has to accommodate IL-9, IL-10, IL-13, TNF-α, IL-12, and IL-18. Importantly, resistance to infection is not just about making an appropriate type 2 response. Effector cells have to be recruited locally to the site of infection in order to culminate in worm expulsion, which brings new key players into our model, including chemokines.

Keywords:

• Trichuris muris
• Cytokine
• Chemokine
• Th1
• Th2