Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies

Abstract

Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.

Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens

“…IL-10-producing FoxP3 ϩ regulatory CD4 T cells have been detected in parasite infections, including those caused by T. cruzi (2), L. major (5), L. guyanensis (10), T. gondii (95), and P. yoelii (19), although the exact mechanism of their action has not been fully elucidated. For L. major, IL-10-producing CD4 ϩ CD25 ϩ FoxP3 ϩ T cells have been shown to inhibit the generation of memory recall immunity upon challenge with heat-killed parasites (93,94), indicating that IL-10-producing CD4 T cells can have a detrimental impact on immune responses, at least for the functional capacity of memory recall responses. IL-10 is also found within CD4 FoxP3…”

Recurrent Visceral Leishmaniasis in an Immunocompetent Patient: A Case Report.

“…Secretion of proinflammatory Th1-type cytokines such as interferon-γ, interleukin-12 and tumor necrosis factor-α prevents parasitemia and development of chronic disease. On the contrary, in immunosuppressed patients, immune responses are ineffective and dissemination of disease occurs frequently [7].…”

Vaccines for the Leishmaniases: Proposals for a Research Agenda

“…The challenge will be to achieve attenuation of live parasites without losing efficacy. In this regard, observations in animal models indicate that antigen persistence may be as important as the specific protein or parasite component employed in a vaccine [30].…”