Chronic Giardiasis in CBA/N Mice: Use of Genetically Immunodeficient Mice to Study Mechanisms of Immunity to an Intestinal Parasite

Abstract

<p>Giardia muris is an intestinal parasite of mice. It has a simple life cycle and is non-invasive. Therefore, G. muris infection provides a model to study immune mechanisms that operate at mucosal surfaces. Immunocompetent mice eliminate primary G. muris infections. T cell-dependent humoral immune mechanisms are involved in this process.</p> <p>The CBA/N mouse bears an X-linked immunodeficiency gene (Xid), the expression of which results in defective B cell maturation and consequent impairment of certain humoral immune responses. The antibody responses of CBA/N mice are particularly defective in certain isotypes and specificities.</p> <p>CBA/N mice fail to eliminate G. muris. The major focus of this dissertation was an attempt to elucidate the basis for chronic giardiasis in this strain.</p> <p>Cellular reconstitution experiments showed that the ability to eliminate G. muris was transferred to CBA/N mice with lymphoid cells from immunocompetent, CBA/Ca mice. Reconstitution required prior irradiation of recipient mice, and was not effective with semi-purified B cells and T cells. These results indicate that conventional B cells and T cells are insufficient, and that another cell type is also required. This cell may be the Lyl+ B cell.</p> <p>CBA/N mice make quantitatively deficient serum IgG antibody responses to G. muds infection. Providing CBA/N mice with this antibody failed to induce elimination of the parasite, thus this isotype defect was ruled out as the cause of their susceptibility to chronic giardiasis.</p> <p>Analysis of G. muris antigen recognition failed to reveal a specificity defect in the antibody response of CBA/N mice. However, a glycolipid component of G. muris bound serum IgM from CBA/J and BALB/c mice, but not serum IgM from CBA/N mice. These results indicate a possible structural defect in IgM from CBA/N mice.</p> <p>Although unable to eliminate primary G. muris infection, drug-cured CBA/N mice are resistant to reinfection. These results indicate that the immune mechanisms that mediate elimination of G. muris are different from those that mediate resistance to reinfection.</p>