NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia

Simple item page
dc.contributor.authorCnops, Jenniferen_ZA
dc.contributor.authorTrez, Carl Deen_ZA
dc.contributor.authorStijlemans, Benoiten_ZA
dc.contributor.authorKeirsse, Jirien_ZA
dc.contributor.authorKauffmann, Florenceen_ZA
dc.contributor.authorBarkhuizen, Marken_ZA
dc.contributor.authorKeeton, Roanneen_ZA
dc.contributor.authorBoon, Louisen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.contributor.authorMagez, Stefanen_ZA
dc.date.accessioned2015-12-28T06:51:16Z
dc.date.available2015-12-28T06:51:16Z
dc.date.issued2015en_ZA
dc.description.abstractAfrican trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia.en_ZA
dc.identifier.apacitationCnops, J., Trez, C. D., Stijlemans, B., Keirsse, J., Kauffmann, F., Barkhuizen, M., ... Magez, S. (2015). NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia. <i>PLoS One</i>, http://hdl.handle.net/11427/16065en_ZA
dc.identifier.chicagocitationCnops, Jennifer, Carl De Trez, Benoit Stijlemans, Jiri Keirsse, Florence Kauffmann, Mark Barkhuizen, Roanne Keeton, Louis Boon, Frank Brombacher, and Stefan Magez "NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/16065en_ZA
dc.identifier.citationCnops, J., De Trez, C., Stijlemans, B., Keirsse, J., Kauffmann, F., Barkhuizen, M., ... & Magez, S. (2015). NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia. PLoS pathogens, 11(6). doi:10.1371/journal.ppat.1004964en_ZA
dc.identifier.ris TY - Journal Article AU - Cnops, Jennifer AU - Trez, Carl De AU - Stijlemans, Benoit AU - Keirsse, Jiri AU - Kauffmann, Florence AU - Barkhuizen, Mark AU - Keeton, Roanne AU - Boon, Louis AU - Brombacher, Frank AU - Magez, Stefan AB - African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia. DA - 2015 DB - OpenUCT DO - 10.1371/journal.ppat.1004964 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia TI - NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia UR - http://hdl.handle.net/11427/16065 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16065
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1004964
dc.identifier.vancouvercitationCnops J, Trez CD, Stijlemans B, Keirsse J, Kauffmann F, Barkhuizen M, et al. NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia. PLoS One. 2015; http://hdl.handle.net/11427/16065.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the <a href=en_ZA
dc.rights.holder© 2015 Cnops et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherAnemiaen_ZA
dc.subject.otherCytotoxic T cellsen_ZA
dc.subject.otherSpleenen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherBone marrow cellsen_ZA
dc.subject.otherCloningen_ZA
dc.subject.otherInflammationen_ZA
dc.titleNK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemiaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Cnops_NK_NKT_and_CD8_2015.pdf
Size:
2.25 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles