Mechanisms for Establishing Persistence: Immune Modulation

Abstract

This chapter examines the increasingly common scenarios in which bacteria actively modulate the immune response to ensure their persistence. The mechanisms of protection against infectious agents may be divided into two complementary components: innate, or natural, immunity and specific, or acquired, immunity. It is important to mention that nonprotein antigens, such as microbial (particularly mycobacterial) lipid and glycolipid antigens, can be presented to T cells in a restricted fashion by nonclassical major histocompatibility complex (MHC) molecules, such as CD1, that are differentially expressed on antigen-presenting cells (APC) and cells of the gastrointestinal epithelium. Inhibition of mitogen-induced lymphocyte proliferation by whole live bacteria, soluble or particulate preparations of the bacteria, and sometimes purified molecules is arguably the most common observation in the literature concerning inhibition of the host's immune response. The induction of apoptosis in monocytes/macrophages has been shown to be triggered by a number of bacteria or purified bacterial products in vivo, as well as in vitro in primary and short-term cultures. Through an in-depth examination of the mechanisms used by the microbial adversaries to evade or otherwise subvert the host's immune response, we may be able to devise more effective live vaccines and develop novel therapeutic strategies for the treatment of persistent infections, as well as to discover valuable immunomodulatory agents.