Leptospirosis renal disease: understanding the initiation by Toll-like receptors

Leptospirosis is a prevalent infectious disease affecting both humans and animals worldwide. This infection is associated with occupational or recreational exposure to animals as well as contact with leptospires, particularly in flood-prone areas. Multiple organ dysfunctions may be associated with acute severe leptospirosis. A triad presentation of fever, jaundice, and acute renal failure in patients with acute multiple organ dysfunction should alert physicians to possible leptospirosis. Penicillin is effective and can rescue multiple organ failure if administered early. Renal involvement is common in leptospirosis characterized by tubulo-interstitial nephritis, and tubular dysfunction. Leptospira outer membrane proteins (OMPs) may elicit tubular injury and inflammation through Toll-like receptors (TLRs)-dependent pathway followed by activation of nuclear transcription factor kappa B and mitogen-activated protein kinases and a differential induction of chemokines and cytokines relevant to tubular inflammation. Leptospira OMP may also induce activation of the transforming growth factor-beta/Smad-associated fibrosis pathway leading to accumulation of extracellular matrix. Thus, leptospirosis renal disease is a model for understanding the pathogenesis and initiation of pathogen-induced tubulo-interstitial nephritis and fibrosis. In particular, TLRs may be important mediators.