The protozoan parasite Leishmania donovani, residing and replicating within the cells of the monocyte-macrophage (mono-mac) lineage, causes
visceral leishmaniasis (VL) in humans. While, Leishmania infantum, is the main causative agent for zoonotic VL, where dogs are the main reservoirs of the disease. The
chemotherapy is a serious problem because of restricted repertoire of drugs,
drug-resistant parasites,
drug-toxicity and the requirement for parenteral administration, which is a problem in resource-starved countries. Moreover, immunocompromised individuals, particularly HIV-1 infected are at higher risk of VL due to impairment in T-helper cell and regulatory cell responses. Furthermore, HIV-VL co-infected patients report poor response to conventional
chemotherapy. Recent efforts are therefore directed towards devising both prophylactic and therapeutic
immunomodulation. As far as prophylaxis is concerned, although canine
vaccines for the disease caused by Leishmania infantum or Leishmania chagasi are available, no
vaccine is available for use in humans till date. Therefore, anti-leishmanial
immunotherapy triggering or manipulating the host's immune response is gaining momentum during the last two decades.
Immunomodulators comprised of small molecules, anti-leishmanial
peptides, complex
ligands for host
receptors, cytokines or their agonists and
antibodies have been given trials both in experimental models and in humans. However, the success of
immunotherapy in humans remains a far-off target. We, therefore, propose that devising a successful
immunotherapy is an act of balancing enhanced beneficial Leishmania-specific responses and deleterious immune activation/hyperinflammation just as the swings in a trapeze.