Continual renewal and replication of persistent<i>Leishmania major</i>parasites in concomitantly immune hosts

Mandell, Michael A.; Beverley, Stephen M.

doi:10.1073/pnas.1619265114

Cited by 103 publications

(113 citation statements)

References 76 publications

(91 reference statements)

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“…Several approaches have been established to determine pathogen proliferation in vivo. For Leishmania spp., heavy water labeling [57] and in vivo BrdU labeling [63] have been used to identify proliferating parasites by dilution of deuterium isotopes or by DNA synthesis, respectively. However, these approaches had only limited compatibility with single-cell analysis and antibody staining and did not permit in vivo validation of the readout through side-by-side comparison with the actual cell division events.…”

Section: Discussionmentioning

confidence: 99%

Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils

Hurrell

Beaumann

Heyde

et al. 2017

Journal of Leukocyte Biology

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Cutaneous leishmaniasis is a neglected tropical disease, causing a spectrum of clinical manifestations varying from self-healing to unhealing lesions that may be very difficult to treat. Emerging evidence points to a detrimental role for neutrophils during the first hours following infection with many distinct species (spp.) at a time when the parasite is in its nonreplicative promastigote form. Neutrophils have also been detected at later stages of infection in unhealing chronic cutaneous lesions. However, the interactions between these cells and the replicative intracellular amastigote form of the parasite have been poorly studied. Here, we show that amastigotes are efficiently internalized by neutrophils and that this process has only a low impact on neutrophil activation and apoptosis. In neutrophils, the amastigotes were found in acidified vesicles. Furthermore, within cutaneous unhealing lesions, heavily infected neutrophils were found with up to 6 parasites per cell. To investigate if the amastigotes could replicate within neutrophils, we generated photoconvertible fluorescent parasites. With the use of flow cytometry imaging and time-lapse microscopy, we could demonstrate that a subset of parasites replicated within neutrophils. Overall, our data reveal a novel role for neutrophils that can act as a niche for parasite replication during the chronic phase of infection, thereby contributing to disease pathology.

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Section: Discussionmentioning

confidence: 99%

Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils

Hurrell

Beaumann

Heyde

et al. 2017

Journal of Leukocyte Biology

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“…Macrophages are one of the primary cell types that exert microbicidal activity against several groups microorganisms via polarization and duality of the response between the M1 and M2 phenotypes. [144][145][146] Therefore, an intriguing relationship is established in infectious diseases due to what happens intracellularly. [144][145][146] Classically, iNOS and Arg1 are characteristic and determinant markers for modulating the response of either M1 (iNOS) or M2 (Arg1) macrophages.…”

Section: Markers Of M1 M2 and M4 Macrophagesmentioning

confidence: 99%

“…[144][145][146] Therefore, an intriguing relationship is established in infectious diseases due to what happens intracellularly. [144][145][146] Classically, iNOS and Arg1 are characteristic and determinant markers for modulating the response of either M1 (iNOS) or M2 (Arg1) macrophages. [147][148][149] The resulting effects of these enzymes demonstrate that both compete for the same substrate (arginine) in order to induce the production of NO (M1) or proliamines and proline (M2).…”

Section: Markers Of M1 M2 and M4 Macrophagesmentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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“…Future experiments should thus reveal the mechanisms of persistent haemoplasma infection. In particular, it is important to understand whether (a) the low stable infection levels result from the bacterium's or the mammalian host's actions, (b) the bacterium hides in other tissues in the rodent's body (Novacco, Riond, Meli, Grest, & Hofmann-Lehmann, 2013;Tasker et al, 2009a;Wolf-Jäckel et al, 2012), and (c) the bacterium replicates during the stabilized infection period or remains in a dormant state (Mandell & Beverley, 2017;Monack & Hultgren, 2013;Potgieter, Bester, Kell, & Pretorius, 2015;Vadivelu et al, 2017).…”

Section: Infection Dynamicsmentioning

confidence: 99%

Haemoplasmas in wild rodents: Routes of transmission and infection dynamics

et al. 2018

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The way that some parasites and pathogens persist in the hostile environment of their host for long periods remains to be resolved. Here, longitudinal field surveys were combined with laboratory experiments to investigate the routes of transmission and infection dynamics of such a pathogen-a wild rodent haemotropic bacterium, specifically a Mycoplasma haemomuris-like bacterium. Fleaborne transmission, direct rodent-to-rodent transmission and vertical transmission from fleas or rodents to their offspring were experimentally quantified, and indications were found that the main route of bacterial transmission is direct, although its rate of successful transmission is low (~20%). The bacterium's temporal dynamics was then compared in the field to that observed under a controlled infection experiment in field-infected and laboratory-infected rodents, and indications were found, under all conditions, that the bacterium reached its peak infection level after 25-45 days and then decreased to low bacterial loads, which persist for the rodent's lifetime. These findings suggest that the bacterium relies on persistency with low bacterial loads for long-term coexistence with its rodent host, having both conceptual and applied implications.

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Continual renewal and replication of persistentLeishmania majorparasites in concomitantly immune hosts

Cited by 103 publications

References 76 publications

Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils

Frontline Science: Leishmania mexicana amastigotes can replicate within neutrophils

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Haemoplasmas in wild rodents: Routes of transmission and infection dynamics

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