title: Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection.
abstract: Myeloperoxidase (MPO), a leukocyte-derived enzyme mainly secreted by activated neutrophils, is known to be involved in the immune response during bacterial and fungal infection and inflammatory diseases. Nevertheless, the role of MPO in a parasitic disease like malaria is unknown. We hypothesized that MPO contributes to parasite clearance. To address this hypothesis, we used Plasmodium yoelii nonlethal infection in wild-type and MPO-deficient mice as a murine malaria model. We detected high MPO plasma levels in wild-type mice with Plasmodium yoelii infection. Unexpectedly, infected MPO-deficient mice did not show increased parasite loads but were able to clear the infection more rapidly than wild-type mice. Additionally, the presence of neutrophils at the onset of infection seemed not to be essential for the control of the parasitemia. The effect of decreased parasite levels in MPO-deficient mice was absent from animals lacking mature T and B cells, indicating that this effect is most likely dependent on adaptive immune response mechanisms. Indeed, we observed increased gamma interferon and tumor necrosis factor alpha production by T cells in infected MPO-deficient mice. Together, these results suggest that MPO modulates the adaptive immune response during malaria infection, leading to an attenuated parasite clearance.
authors: Bernhard-Nocht Institute for Tropical Medicine, Clinical Research Group, Hamburg, Germany.|University Medical Center Hamburg-Eppendorf, I. Department of Medicine, Section Tropical Medicine, Hamburg, Germany.
authors: Wiebke
authors: W
authors: Theeß
authors: Bernhard-Nocht Institute for Tropical Medicine, Department of Immunology, Hamburg, Germany.
authors: Julie
authors: J
authors: Sellau
authors: Bernhard-Nocht Institute for Tropical Medicine, Department of Immunology, Hamburg, Germany.
authors: Christiane
authors: C
authors: Steeg
authors: Heart Center, Department of Cardiology, University of Cologne, Cologne, Germany.
authors: Anna
authors: A
authors: Klinke
authors: Heart Center, Department of Cardiology, University of Cologne, Cologne, Germany.
authors: Stephan
authors: S
authors: Baldus
authors: Bernhard-Nocht Institute for Tropical Medicine, Clinical Research Group, Hamburg, Germany.|University Medical Center Hamburg-Eppendorf, I. Department of Medicine, Section Tropical Medicine, Hamburg, Germany.
authors: Jakob P
authors: JP
authors: Cramer
authors: Bernhard-Nocht Institute for Tropical Medicine, Department of Immunology, Hamburg, Germany tjacobs@bni-hamburg.de.
authors: Thomas
authors: T
authors: Jacobs
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018512:Parasitemia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009195:Peroxidase / Q000276:immunology* / Q000378:metabolism*; D010967:Plasmodium yoelii / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D007371:Interferon-gamma; D009195:Peroxidase
keywords: Plasmodium; T-cell immunity; T-lymphocytes; animal disease model; cytokines; immunology; innate immunity; knockout mice; malaria; neutrophils; peroxidase