DH82 Canine and RAW264.7 Murine Macrophage Cell Lines Display Distinct Activation Profiles Upon Interaction With Leishmania infantum and Leishmania amazonensis (original) (raw)
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Leishmania parasites are digenetic protozoans which infect human hosts and are causative agents of a series of diseases known under the name of leishmaniasis. Macrophages represent the main host. Hence the interaction between Leishmania and macrophages is a fundamental step in the development of the disease. Many studies have been undertaken to understand early stages of the parasite interaction with macrophages; however, few have investigated the later stages of infection. This study was undertaken to develop an experimental model to examine the fate of the parasites when they leave the safe environment represented by their host macrophage. Primarily, the study investigated how Leishmania spread to neighbouring cells without being recognized and killed by the immune system defences. Three Old World species of Leishmania parasites: L. aethiopica, L. major and L. tropica, all responsible for the cutaneous form of the disease, were used. A model of infection was described using two ce...
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Cytokine: X, 2020
Leishmania are protozoan parasites that predominantly reside in myeloid cells within their mammalian hosts. Monocytes and macrophages play a central role in the pathogenesis of all forms of leishmaniasis, including cutaneous and visceral leishmaniasis. The present review will highlight the diverse roles of macrophages in leishmaniasis as initial replicative niche, antimicrobial effectors, immunoregulators and as safe hideaway for parasites persisting after clinical cure. These multiplex activities are either ascribed to defined subpopulations of macrophages (e.g., Ly6C high CCR2 + inflammatory monocytes/monocyte-derived dendritic cells) or result from different activation statuses of tissue macrophages (e.g., macrophages carrying markers of of classical [M1] or alternative activation [M2]). The latter are shaped by immune-and stromal cell-derived cytokines (e.g., IFN-γ, IL-4, IL-10, TGF-β), micro milieu factors (e.g., hypoxia, tonicity, amino acid availability), host cell-derived enzymes, secretory products and metabolites (e.g., heme oxygenase-1, arginase 1, indoleamine 2,3-dioxygenase, NOS2/NO, NOX2/ROS, lipids) as well as by parasite products (e.g., leishmanolysin/gp63, lipophosphoglycan). Exciting avenues of current research address the transcriptional, epigenetic and translational reprogramming of macrophages in a Leishmania species-and tissue context-dependent manner.
Leishmania amazonensis and macrophage interactions: immune factors necessary to kill the parasite
List of Tables vi List of Figures vii CHAPTER 1 General Introduction V 2.4.7 Glutathione 3. Host immune response to Leishmania 3.1 CD4 + T cells and L. major infection 3.2 CD4 + T cells and L. amazonensis 3.3 B cells 4. General conclusion References CHAPTER 2 Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide Abstract Introduction Material and methods Results Discussion References CHAPTER 3 Leishmania major specific CD4 + T cells and B cells limit L. amazonensis amastigote survival within in vitro infected macrophages through IgG mediated superoxide production Abstract Introduction Material and methods Results Discussion References CHAPTER 4 Leishmania infection modulates the expression of Fey receptors Abstract CHAPTER 2 Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide
Experimental Parasitology, 1992
amazonensis infection: A comparison of in vivo leishmanicidal mechanisms between immunized and naive infected BALBlc mice. Experimental Parasitology 74, 169-176. In vitro studies have shown that both macrophage activation and destruction of parasitized macrophages lead to leishmania destruction. The relative role played by such mechanisms in vivo have not been properly evaluated. We took advantage of the model of intravenous immunization with solubilized leishmanial antigen which renders partially resistant the otherwise highly susceptible BALB/c mice to address this issue avoiding the interference of different genetic backgrounds. Leishmania destruction occurred in three situations: destruction of the parasitized macrophage, which were in close contact with lymphocytes or eosinophils; extracellular damage, always surrounded by small foci of granulocytes; and parasite damage inside activated macrophages. Destruction of the parasitized macrophages was frequently seen in immunized and protected animals. Our observations suggest that destruction of parasite-loaded macrophages is an important mechanism of host protection in experimental cutaneous leishmaniasis. 0 19% Academic PESS, IX.
Cytokine Gene Expression Alterations in Human Macrophages Infected by Leishmania major
Cell J. 2021; 22(4): 476-481., 2021
Objective: Leishmaniasis is caused by members of the Leishmania species and constitute a group of infective diseases that range from cutaneous lesions to lethal visceral forms. In infected persons, macrophages recognize and eliminate the parasites via phagocytosis. In order to change a hostile environment into an environment adequate for survival and reproduction, the engulfed Leishmania species needs to modulate the function of its host macrophage. The expression patterns of cytokine genes such as interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-α), IL-1, and interferon-gamma (IFNγ) represent the immune response. In this study, we employed an RNA-seq approach for human monocyte-derived macrophages infected with Leishmania major (L. major) to decipher cytokine gene expression alterations in host macrophages. Materials and Methods: In this descriptive study, human monocytes were isolated by magnetic activated cell sorting (MACS) and cultured in the presence of monocyte colony stimulating factor (M-CSF) to obtain the macrophages. Monocyte-derived macrophages were then co-cultured with metacyclic promastigotes of L. major for 4 hours. RNA isolation was performed using TRIzol reagent. RNA sequencing was performed using the Illumina sequencing platforms. Gene expression analysis was performed using a Bioconductor DESeq2 package. Results: Our data revealed significant changes in immune response gene expressions in macrophages infected with L. major, with an up-regulation of cytokines and mostly down-regulation of their receptors. Conclusion: The obtained data could shed more light on the biology of L. major and how the host cell responds to leishmaniasis.
BMC Microbiology, 2012
Background The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite. Results The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that ...
European Journal of Immunology, 1995
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