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      Role of Cytokines in Experimental and Human Visceral Leishmaniasis

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          Abstract

          Visceral Leishmaniasis (VL) is the most fatal form of disease leishmaniasis. To date, there are no effective prophylactic measures and therapeutics available against VL. Recently, new immunotherapy-based approaches have been established for the management of VL. Cytokines, which are predominantly produced by helper T cells (Th) and macrophages, have received great attention that could be an effective immunotherapeutic approach for the treatment of human VL. Cytokines play a key role in forming the host immune response and in managing the formation of protective and non-protective immunities during infection. Furthermore, immune response mediated through different cytokines varies from different host or animal models. Various cytokines viz. IFN-γ, IL-2, IL-12, and TNF-α play an important role during protection, while some other cytokines viz. IL-10, IL-6, IL-17, TGF-β, and others are associated with disease progression. Therefore, comprehensive knowledge of cytokine response and their interaction with various immune cells is very crucial to determine appropriate immunotherapies for VL. Here, we have discussed the role of cytokines involved in VL disease progression or host protection in different animal models and humans that will determine the clinical outcome of VL and open the path for the development of rapid and accurate diagnostic tools as well as therapeutic interventions against VL.

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          Most cited references196

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          Differentiation of effector CD4 T cell populations (*).

          CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.
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            Leishmaniasis: complexity at the host-pathogen interface.

            Leishmania is a genus of protozoan parasites that are transmitted by the bite of phlebotomine sandflies and give rise to a range of diseases (collectively known as leishmaniases) that affect over 150 million people worldwide. Cellular immune mechanisms have a major role in the control of infections with all Leishmania spp. However, as discussed in this Review, recent evidence suggests that each host-pathogen combination evokes different solutions to the problems of parasite establishment, survival and persistence. Understanding the extent of this diversity will be increasingly important in ensuring the development of broadly applicable vaccines, drugs and immunotherapeutic interventions.
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              Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

              Secondary lymphoid organ chemokine (SLC) is expressed in high endothelial venules and in T cell zones of spleen and lymph nodes (LNs) and strongly attracts naive T cells. In mice homozygous for the paucity of lymph node T cell (plt) mutation, naive T cells fail to home to LNs or the lymphoid regions of spleen. Here we demonstrate that expression of SLC is undetectable in plt mice. In addition to the defect in T cell homing, we demonstrate that dendritic cells (DCs) fail to accumulate in spleen and LN T cell zones of plt mice. DC migration to LNs after contact sensitization is also substantially reduced. The physiologic significance of these abnormalities in plt mice is indicated by a markedly increased sensitivity to infection with murine hepatitis virus. The plt mutation maps to the SLC locus; however, the sequence of SLC introns and exons in plt mice is normal. These findings suggest that the abnormalities in plt mice are due to a genetic defect in the expression of SLC and that SLC mediates the entry of naive T cells and antigen-stimulated DCs into the T cell zones of secondary lymphoid organs.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                18 February 2021
                2021
                : 11
                : 624009
                Affiliations
                [1] 1 Cell and Molecular Biology Laboratory, Department of Zoology, Kumaun University , Almora, India
                [2] 2 Department of Microbiology, All India Institute of Medical Sciences , Bhopal, India
                Author notes

                Edited by: Rajiv Kumar, Banaras Hindu University, India

                Reviewed by: Sreenivas Gannavaram, United States Food and Drug Administration, United States; Rakesh K. Singh, Banaras Hindu University, India

                This article was submitted to Parasite and Host, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2021.624009
                7930837
                33680991
                a165b6cd-69af-4d70-b22e-fa2c8af2cac1
                Copyright © 2021 Samant, Sahu, Pandey and Khare

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 October 2020
                : 22 January 2021
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 196, Pages: 18, Words: 11092
                Funding
                Funded by: Department of Biotechnology, Ministry of Science and Technology, India 10.13039/501100001407
                Categories
                Cellular and Infection Microbiology
                Review

                Infectious disease & Microbiology
                visceral leishmaniasis,animal models,human,cytokine response,immunotherapy

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