Antibody Immunity and Natural Resistance to Cryptococcosis

Purpose of Review: To review recent data on the role that B cells and/or antibody-based immunity play in host defense against Cryptococcus neoformans (Cn). Recent Findings: Cn, an encapsulated fungus, causes cryptococcal meningitis (CM). There are ~180,000 deaths per year worldwide attributed to CM, which is the most common cause of meningitis in adults with HIV in sub-Saharan Africa. HIV infection with advanced immunodeficiency is the most important predisposing risk factor for CM, highlighting the critical role that T cell-mediated immunity plays in disease prevention. However, numerous studies in the past decade demonstrate that antibody immunity also plays a role in resistance to CM. In mice, B cells reduce early dissemination from the lungs to the brain, and naïve mouse IgM can enhance fungal containment in the lungs. In concert with these findings, human studies show that patients with CM have lower IgM memory B cell levels and/or different serum profiles of Cn-binding and natural antibodies than controls. Summary: There is sufficient evidence to support a possible role for B cells and certain antibodies in natural resistance to CM. This underscores the need for a deeper understanding of mechanisms by which natural and Cn-binding antibodies may reduce Cn virulence and protect against Cn dissemination and human CM.