Immune response to leishmania: paradox rather than paradigm

Abstract

The leishmaniases are a group of diseases caused by protozoan parasites of the genus Leishmania. Various Leishmania species can cause human infection, producing a spectrum of clinical manifestations. It is estimated that 350 million people are at risk, with a global yearly incidence of 1-1.5 million for cutaneous and 500,000 for visceral leishmaniasis (VL). VL is a major cause of morbidity and mortality in East Africa and the Indian subcontinent. Coinfection with HIV enhances the risk of the disease. The only control measure currently available in India is case detection and treatment with antimonial drugs, which are expensive, not always available and cannot be self-administered. Newer drugs like oral miltefosine have not become widely available. Vector and reservoir control is difficult due to the elusive nature of the vector and the diversity of the animal reservoir. A detailed knowledge of immune response to the parasite would help in designing prophylactic and therapeutic strategies against this infection.

Comparative immune study on cutaneous leishmaniasis patients with single and multiple sores

“…In both human and experimental models of CL, control of infection is mediated by T-lymphocytes and is critically dependent upon the early induction of an IL-12-driven Th-1 type immune response and the production of IFN-c by CD4 T cells (Rosas et al 2005;Tripathi et al 2007).…”

“…IL-4 is the signature cytokine associated with Th2-type immune responses and is associated with non healing forms of cutaneous disease in mice (Tripathi et al 2007). …”

“…IL-4 also functions as a powerful inhibitor of IFN-c-producing CD4 T cells and suppressor of protective Th-1 immune responses (Nelms et al 1998), this fact corresponded with our results of low levels of IFN-c and the high levels of IL-4 in early infection with CL. IL-4, along with related cytokine IL-13, trigger macrophages to undergo alternative activation and is associated with parasite survival and persistence of infection (Rosas et al 2003;Tripathi et al 2007). CL is characterized by a mixed Th-1/Th-2 immune response during the early phase then Th-2 is detected and converts to an evident Th-1 type of immune response documented by lymphocyte proliferation and IFN-c secretion.…”

Protective immunity using MPL-A and autoclaved Leishmania donovani as adjuvants along with a cocktail vaccine in murine model of visceral leishmaniasis

“…In contrast, IL-10 response was found to be maximum in infected control animals but declined significantly in mice immunized with gp63?Hsp70?ALD followed by mice immunized with gp63?Hsp70?MPL-A. IL-10 represents the main macrophage-deactivating cytokine and plays an important regulatory role in the progression of VL (Tripathi et al 2007). Our results are in consistence with those obtained from murine leishmaniasis model of both cutaneous and visceral diseases where expression of IFN-c is associated with control of infection (Heinzel et al 1989;Squires et al 1989).…”

Proteases de Leishmania: novos alvos para o desenvolvimento racional de fármacos

“…Dentre as infecções oportunistas que acometem os portadores do HIV, a coinfecção com Leishmania é considerada como a que evolui mais rapidamente para casos fatais. 26 No nordeste do Brasil é observada a transmissão do parasito entre indivíduos, através de sangue contaminado, em bancos sangues e unidades hospitalares.…”