TY - JOUR
T1 - Phagocytosis of hemozoin by RAW 264.7 cells, but not THP-1 cells, promotes infection by Leishmania donovani with a nitric oxide-independent mechanism
AU - van den Bogaart, Erika
AU - Mens, Pètra F.
AU - Adams, Emily R.
AU - Grobusch, Martin P.
AU - Schallig, Henk D. F. H.
PY - 2017
Y1 - 2017
N2 - During its intra-erythrocytic development, the malaria 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 48h after phagocytosis. Conditioning with lipopolysaccharide (LPS)/interferon (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
AB - During its intra-erythrocytic development, the malaria 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 48h after phagocytosis. Conditioning with lipopolysaccharide (LPS)/interferon (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
U2 - https://doi.org/10.1016/j.parint.2016.09.003
DO - https://doi.org/10.1016/j.parint.2016.09.003
M3 - Article
C2 - 27623326
SN - 1383-5769
VL - 66
SP - 196
EP - 206
JO - Parasitology international
JF - Parasitology international
IS - 2
ER -