MECHANISM OF ACTION OF ANTIBODY TO CAPSULAR POLYSACCHARIDE IN CRYPTOCOCCUS NEOFORMANS INFECTION

Marta Feldmesser¹ and Arturo Casadevall^1,2

1Departments of Medicine (Division of Infectious Diseases) and Microbiology and Immunology², Albert Einstein College of Medicine, Golding Building Room 701, 1300 Morris Park Ave., Bronx, NY 10461

Received 1/5/98 Accepted 1/9/98

1. ABSTRACT

Cryptococcus neoformans is an encapsulated fungus that causes meningoencephalitis in 5-10% of patients with AIDS. While the immune response that controls infection is predominantly cell-mediated, Ab-mediated immunity is being studied for therapeutic use. mAbs to glucuronoxylomannan (GXM), the predominant constituent of the polysaccharide capsule are protective in a variety of murine infection models. However, the mechanism of Ab action in this infection is unknown. We review the literature on the effect of Ab in cryptococcal infection and potential mechanisms of action. The mechanism is likely multifactorial, involving enhancement at several branches of the immune response, including opsonization, antigen presentation and altered effector cell function. Removal of the toxic and immunosuppressive effects of GXM may be an important component of the mechanism of Ab action. Changes in pathology in response to monoclonal antibody (mAb) administration suggest that alterations in cytokine production may mediate mAb effects. In summary, specific Ab can modulate the course of cryptococcal infection to the benefit or detriment of the host, but significant questions remain concerning the mechanism of action and the relative importance of antibody-mediated immunity in normal and immunocompromised hosts.