About this Research Topic
Commonly considered as one of the major hallmarks of the adaptive immune system, immunologic memory provides the organism with long-lasting and robust protection against reinfection and is the basis for vaccination against infectious diseases. It is mediated by memory T and B cells that arise from expansion and differentiation of naïve cells during a primary immune response. Memory cells are endowed with prolonged life and self-renewing properties and enhanced specific antigen (Ag) recognition.
Memory T cells (CD4+ and CD8+) have been associated with resistance to cutaneous and visceral leishmaniasis, regardless of the species of parasite involved. A persisting antigen or pathogen is crucial for the expansion of naive antigen-specific CD4+ and CD8+ T cells that give rise to effector and memory cells. In the same way, persistence of Leishmania parasites has been shown to occur, but there is no consensus if this parasite persistence is responsible for maintenance of long-term memory cells. It is known that effector CD4+ T cells are lost in the absence of parasites, although maintenance of central memory CD4+ T cells appears to be independent of persistent parasites. It is believed that upon secondary infection, these central memory T cells become effector T-cells that mediate rapid protection by production of cytokines such as IFN-g and TNF that are critical for the activation of macrophages leading to parasite killing. CD8+ T cells also play a role in host protection and are required for the effective clearance of parasites.
The natural history of tegumentary leishmaniasis indicates that after lesion resolution individuals acquire long-lasting immunity and reinfection is uncommon. In comparison to visceral leishmaniasis, subversion of the host antigen-presenting cells (APCs) activities and consequent T cell dysfunction mark the disease. Effective primary anti-Leishmania immunity requires both innate and adaptive immune responses and involves effective activation of macrophages, dendritic cells (DC), and antigen-specific CD4+ and CD8+ T cells. The induction of Th1 type immune response and phagocyte activation ensures higher chances to cure.
Despite advances, the development of safe and effective vaccines for long-lasting protection against leishmaniasis is still a challenge. Various studies have shown that induction of single, polyfunctional T cells leads to better vaccine-induced protection. Therefore, the major obstacles in vaccine development are to characterize the long-lasting protective immunity and to devise safe and effective strategies to achieve this goal. To date, there is no real measure that can prevent the spread of leishmaniasis worldwide. In particular, there is no effective vaccine against the disease. This is in part due to inadequate understanding of the mechanisms of protective immunity, particularly those associated with memory response. We believe that increased understanding of the immune response triggered by different species of Leishmania, particularly those associated with memory response, is the key to finding and developing an effective vaccine against the disease.
This Research Topic explores our understanding and knowledge about the correlates of protective memory immunity in leishmaniasis, which may be useful for development of effective vaccines and vaccination strategies against leishmaniasis. We welcome the submission of Original Research on in vitro and in vivo studies, Reviews, Mini-Reviews, Hypotheses and Theories, and Perspective articles on, but not limited to, the following themes:
• Proposal of new strategies and tools for evaluation or characterization of the immune profile elicited by CD4+ T lymphocytes in leishmaniasis
• Immunomodulation by memory T cells
• Cytokine gene expression/production profile
• Immunophenotyping of memory T cells
• Molecules involved in memory T cell exhaustion in visceral and cutaneous leishmaniasis models
• The role of skin resident memory T cells in cutaneous leishmaniasis
• Influence of sandfly saliva components in the development of long-lasting immune memory against Leishmania
Keywords: Leishmania, Memory T cells, Immunological Memory
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