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Phagocytosis of hemozoin by RAW 264.7 cells, but not THP-1 cells, promotes infection by Leishmania donovani with a nitric oxide-independent mechanism

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van den Bogaart, Erika, Mens, Pètra F, Adams, Emily ORCID: https://orcid.org/0000-0002-0816-2835, Grobusch, Martin P and Schallig, Henk D F H (2017) 'Phagocytosis of hemozoin by RAW 264.7 cells, but not THP-1 cells, promotes infection by Leishmania donovani with a nitric oxide-independent mechanism'. Parasitology international, Vol 66, Issue 2, pp. 196-206.

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Effect of HZ ingestion on L donovani infection Parasitol Int (accepted version with figures).docx - Accepted Version

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Abstract

During its intra-erythrocytic development, the malarial parasite Plasmodium falciparum synthesizes insoluble hemozoin (HZ) crystals that are released into the circulation upon rupture of parasitized red blood cells, and rapidly phagocytized by host mononuclear cells. Here, HZ persists undigested, causing functional impairment and possibly leading to increased host susceptibility to secondary infections. In patients with malaria and visceral leishmaniasis (VL) co-infections, HZ-loaded macrophages are likely to co-harbor Leishmania donovani parasites, but whether this might influence the course of the Leishmania infection is unknown. In this study, L. donovani amastigote growth was monitored in mouse RAW 264.7 macrophages and PMA-differentiated THP-1 cells previously exposed to increasing amounts of HZ or its synthetic analogue β-hematin (BH). Latex beads were used as a phagocytic control. Data demonstrate that phagocytosis of HZ and BH by RAW 264.7 cells promoted infection therein by L. donovani parasites in a dose-dependent fashion. Similar results were not observed when using THP-1 cells, despite a clear persistence of undigested heme up to 48 h after phagocytosis.
Conditioning with lipopolysaccharide (LPS)/interferon-gamma (IFN-γ) prior to Leishmania infection triggered the release in RAW 264.7 cells of nitric oxide (NO), a highly leishmanicidal metabolite. However, neither HZ nor BH pre-ingestion were able to inhibit NO production following stimulation with LPS/IFN-γ, suggesting that the HZ- and BH-promoting effect on L. donovani infection occurred with an NO-independent mechanism. In conclusion, these preliminary findings highlight a possible detrimental effect of HZ on the course of VL, warranting further investigation into the clinical relevance of the current models.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance.
QX Parasitology > Protozoa > QX 135 Plasmodia
QX Parasitology > Protozoa > QX 70 Mastigophora. (e.g., Giardia. Trichomonas. Trypanosoma. Leishmania)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 715 Visceral leishmaniasis
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1016/j.parint.2016.09.003
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 30 Sep 2016 08:58
Last Modified: 15 Jun 2018 09:52
URI: http://archive.lstmed.ac.uk/id/eprint/6183

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