Interaction of Leishmania with the host macrophage

Handman, Emanuela; Bullen, Denise V. R.

doi:10.1016/s1471-4922(02)02352-8

Cited by 178 publications

(137 citation statements)

References 18 publications

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“…Apoptosis-To successfully survive within host cells, L. donovani employs various strategies that render macrophage defense inactive (30). Because apoptosis could be one such means used by macrophages to eliminate intracellular infection, we wanted to see the effect of L. donovani infection on actinomycin D-induced macrophage apoptosis.…”

Section: Leishmania Infection Renders Macrophages Resistant Tomentioning

confidence: 99%

Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis

Giri

Srivastav

Basu

et al. 2016

Journal of Biological Chemistry

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Apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. In the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (MCL-1) is exploited by the intra-macrophage parasite Leishmania donovani to protect their "home" from actinomycin D-induced mitochondria-dependent apoptosis. Among all the anti-apoptotic BCL-2 family members, infection preferentially up-regulated expression of MCL-1 at both the mRNA and protein levels and compared with infected control, MCL-1-silenced infected macrophages documented enhanced caspase activity and increased apoptosis when subjected to actinomycin D treatment. Phosphorylation kinetics and ChIP assay demonstrated that infection-induced MCL-1 expression was regulated by transcription factor CREB (cAMP-response element-binding protein) and silencing of CREB resulted in reduced expression of MCL-1 and increased apoptosis. During infection, MCL-1 was found to be localized in mitochondria and this was significantly reduced in Tom70-silenced macrophages, suggesting the active role of TOM70 in MCL-1 transport. In the mitochondria, MCL-1 interacts with the major pro-apoptotic protein BAK and prevents BAK-BAK homo-oligomer formation thereby preventing cytochrome c release-mediated mitochondrial dysfunction. Silencing of MCL-1 in the spleen of infected mice showed decreased parasite burden and increased induction of splenocyte apoptosis. Collectively our results showed that L. donovani exploited the macrophage anti-apoptotic protein MCL-1 to prevent BAK-mediated mitochondria-dependent apoptosis thereby protecting its niche, which is essential for disease progression.Leishmania donovani, an obligate intracellular parasite, is the causative agent of the fatal visceral leishmaniasis (1). After entry into the macrophages, it survives and replicates inside the acidified phagolysosomes of macrophages (2). Its persistence to resist the host immune system determines the extent of pathogenicity and requires extensive manipulation of macrophage defense (3). One of the vital mechanisms by which host cells defend themselves against intracellular pathogens is the induction of apoptosis (4, 5). On the contrary, pathogens relentlessly try to defeat the host defense systems and evolved a number of ways to inhibit host cell apoptosis, which allows them more time to replicate (6). Various studies have documented the molecular mechanisms in virus (7), bacteria (8), and protozoan parasites (9) that tamper with the host defensive apoptotic machinery. Leishmania, being an obligate intracellular parasite, makes host cells resistant to a variety of pro-apoptotic signals in murine and human cell lines. L. donovani infection protects bone marrow-derived macrophages (BMDM) 2 from growth factor withdrawal-induced apoptosis (10). Infection with Leishmania infantum reduces actinomycin D-induced cell dea...

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Section: Leishmania Infection Renders Macrophages Resistant Tomentioning

confidence: 99%

Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis

Giri

Srivastav

Basu

et al. 2016

Journal of Biological Chemistry

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“…[25][26][27] It is already known that Leishmania parasites have developed a survival mechanism in which they stay viable in phagolysosome after infecting macrophages by receptor-based phagocytosis. 11 In the literature, it has been shown that parasites infect not only professional phagocytotic cells such as macrophages but also amnion epithelial cells, fibroblasts, kidney cells, and dendritic cells in mammalian hosts. 11,12 Furthermore, it is documented that parasites enter these cells by binding different cell surface receptors.…”

Section: Discussionmentioning

confidence: 99%

“…11 In the literature, it has been shown that parasites infect not only professional phagocytotic cells such as macrophages but also amnion epithelial cells, fibroblasts, kidney cells, and dendritic cells in mammalian hosts. 11,12 Furthermore, it is documented that parasites enter these cells by binding different cell surface receptors. Although there are many studies that investigate cellular and molecular characteristics of mesenchymal stem cells, the information about the phagocytic properties of these cells is scarce.…”

Section: Discussionmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stem Cells as a New Host Cell in Latent Leishmaniasis

Allahverdiyev¹,

Bağırova²,

Elcicek³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Some protozoan infections such as Toxoplasma, Cryptosporidium, and Plasmodium can be transmitted through stem cell transplantations. To our knowledge, so far, there is no study about transmission of Leishmania parasites in stem cell transplantation and interactions between parasites and stem cells in vitro. Therefore, the aim of this study was to investigate the interaction between different species of Leishmania parasites and adipose tissue-derived mesenchymal stem cells (ADMSCs). ADMSCs have been isolated, cultured, characterized, and infected with different species of Leishmania parasites (L. donovani, L. major, L. tropica, and L. infantum). Infectivity was examined by Giemsa staining, microculture, and polymerase chain reaction methods. As a result, infectivity of ADMSCs by Leishmania parasites has been determined for the first time in this study. According to our findings, it is very important that donors are screened for Leishmania parasites before stem cell transplantations in regions where leishmaniasis is endemic.

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“…Parasites present in organs such as liver and spleen are not accessible to sand flies. Amastigotes are intracellular parasites found in phagolysosomes of macrophages and other phagocytes [20], and their uptake by the blood-feeding sand fly is assisted by the cutting action of the mouthparts. Thus sand flies are pool feeders, meaning they insert their saw-like mouthparts into the skin and agitate them to produce a small wound into which the blood flows from superficial capillaries [21].…”

Section: The Vectormentioning

confidence: 99%

Leishmaniasis: A Review on Parasite, Vector and Reservoir Host

Alemayehu¹,

Alemayehu²

2017

Health Sci J

129

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Leishmaniasis is a vector-borne disease affecting millions of people worldwide. The disease is caused by different species of Leishmania, and it is manifested by three major clinical forms namely cutaneous, muco-cutaneous and visceral leishmaniasis. This review is aimed to address briefly the parasite, the vector and the reservoir aspects in transmission of leishmaniasis in different regions of the world. The complexity of transmission of the disease lays on the complex life cycle of the parasite which involves sand fly vectors and mammalian reservoirs. The transmission can either be zoonotic and/or anthroponotic through the bite of an infected female sand fly. There is uneven global distribution of the disease often because of the various distribution patterns of the parasite, the vector and the reservoir host species. Various sand fly species in the genus Phlebotomus and Lutzomyia are responsible for transmission of leishmaniasis in the old and new worlds. Animal reservoirs are important for maintaining infections in various areas, and hence are important for zoonotic and rural/sylvatic transmission of the disease. A high prevalence of infection has been reported from small to large domestic and wild mammals. Control and elimination of leishmaniasis require detection of human and animal cases, identification of reservoir hosts, and implementation of effective vector control strategies in areas.

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Interaction of Leishmania with the host macrophage

Cited by 178 publications

References 18 publications

Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis

Leishmania donovani Exploits Myeloid Cell Leukemia 1 (MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis

Adipose Tissue-Derived Mesenchymal Stem Cells as a New Host Cell in Latent Leishmaniasis

Leishmaniasis: A Review on Parasite, Vector and Reservoir Host

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