Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis.
Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activat...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006422&type=printable |
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| author | Belma Melda Abidin Akil Hammami Simona Stäger Krista M Heinonen |
| author_facet | Belma Melda Abidin Akil Hammami Simona Stäger Krista M Heinonen |
| author_sort | Belma Melda Abidin |
| collection | DOAJ |
| description | Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentiation on the persistence of chronic infections is poorly understood. We have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype. Our results further suggest that emergency hematopoiesis contributes to the pathogenesis of visceral leishmaniasis, as decreased HSC expansion results in a lower parasite burden. Conversely, monocytes derived in the presence of soluble factors from the infected bone marrow environment are more permissive to infection by Leishmania. Our results demonstrate that L. donovani is able to subvert host bone marrow emergency responses to facilitate parasite persistence, and put forward hematopoiesis as a novel therapeutic target in chronic infections. |
| format | Article |
| id | doaj-art-b71edb61a7e34c7099f2e7cbfa5e7c40 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-b71edb61a7e34c7099f2e7cbfa5e7c402025-08-20T02:45:28ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-08-01138e100642210.1371/journal.ppat.1006422Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis.Belma Melda AbidinAkil HammamiSimona StägerKrista M HeinonenCells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentiation on the persistence of chronic infections is poorly understood. We have examined here the bone marrow outcome of chronic visceral leishmaniasis and show that the parasite Leishmania donovani induces HSC expansion and skews their differentiation towards non-classical myeloid progenitors with a regulatory phenotype. Our results further suggest that emergency hematopoiesis contributes to the pathogenesis of visceral leishmaniasis, as decreased HSC expansion results in a lower parasite burden. Conversely, monocytes derived in the presence of soluble factors from the infected bone marrow environment are more permissive to infection by Leishmania. Our results demonstrate that L. donovani is able to subvert host bone marrow emergency responses to facilitate parasite persistence, and put forward hematopoiesis as a novel therapeutic target in chronic infections.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006422&type=printable |
| spellingShingle | Belma Melda Abidin Akil Hammami Simona Stäger Krista M Heinonen Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. PLoS Pathogens |
| title | Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. |
| title_full | Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. |
| title_fullStr | Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. |
| title_full_unstemmed | Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. |
| title_short | Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. |
| title_sort | infection adapted emergency hematopoiesis promotes visceral leishmaniasis |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006422&type=printable |
| work_keys_str_mv | AT belmameldaabidin infectionadaptedemergencyhematopoiesispromotesvisceralleishmaniasis AT akilhammami infectionadaptedemergencyhematopoiesispromotesvisceralleishmaniasis AT simonastager infectionadaptedemergencyhematopoiesispromotesvisceralleishmaniasis AT kristamheinonen infectionadaptedemergencyhematopoiesispromotesvisceralleishmaniasis |