Leptospira: Invasion, Pathogenesis and Persistence

Abstract

Leptospirosis is a major public health problem and one of the most widespread zoonotic diseases in the world. The disease is caused by the pathogenic spirochete Leptospira, which induces a wide range of clinical manifestations ranging from mild flu-like illness to severe Weil’s disease characterized by multi-organ failure leading to death. In spite of the fact that this disease has been studied for decades, little is understood regarding mechanisms of pathogenesis, which has hampered the development of novel therapeutic and prophylactic interventions. Recently, development of tools for genetic manipulation as well as publication of genome sequences from both pathogenic and saprophytic leptospires have revealed novel insights into the biology and pathogenesis of this important agent. We discuss recent advances in our understanding of the mechanisms underlying leptospiral invasion and persistence, and factors contributing to evasion of host immunity. The progress made in understanding host responses, particularly the role of innate immune receptors (Toll-like receptors {TLRs}) and cell mediated immune responses are discussed. The potential of Leptospira spp. virulence factors (outer membrane proteins and others) for development of subunit vaccines and the role of adjuvants/immunomoulators in their success are also discussed. Finally, we conclude by highlighting future work that needs to be done in order to better understand the pathogenesis of leptospirosis, thereby paving the way for the development of improved diagnostics and more effective vaccines.