Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures.
The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic t...
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2020
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oai:doaj.org-article:b845d9f70c124f9aaf91dca3f01f76232021-12-02T20:23:49ZSingle cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures.1935-27271935-273510.1371/journal.pntd.0008112https://doaj.org/article/b845d9f70c124f9aaf91dca3f01f76232020-03-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0008112https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFNβ were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection.Yujiao ZhaoMatthew AmodioBrent Vander WykBram GerritsenMahesh M KumarDavid van DijkKevin MoonXiaomei WangAnna MalawistaMonique M RichardsMegan E CahillAnita DesaiJayasree SivadasanManjunatha M VenkataswamyVasanthapuram RaviErol FikrigPriti KumarSteven H KleinsteinSmita KrishnaswamyRuth R MontgomeryPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e0008112 (2020) |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yujiao Zhao Matthew Amodio Brent Vander Wyk Bram Gerritsen Mahesh M Kumar David van Dijk Kevin Moon Xiaomei Wang Anna Malawista Monique M Richards Megan E Cahill Anita Desai Jayasree Sivadasan Manjunatha M Venkataswamy Vasanthapuram Ravi Erol Fikrig Priti Kumar Steven H Kleinstein Smita Krishnaswamy Ruth R Montgomery Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. |
| description |
The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFNβ were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection. |
| format |
article |
| author |
Yujiao Zhao Matthew Amodio Brent Vander Wyk Bram Gerritsen Mahesh M Kumar David van Dijk Kevin Moon Xiaomei Wang Anna Malawista Monique M Richards Megan E Cahill Anita Desai Jayasree Sivadasan Manjunatha M Venkataswamy Vasanthapuram Ravi Erol Fikrig Priti Kumar Steven H Kleinstein Smita Krishnaswamy Ruth R Montgomery |
| author_facet |
Yujiao Zhao Matthew Amodio Brent Vander Wyk Bram Gerritsen Mahesh M Kumar David van Dijk Kevin Moon Xiaomei Wang Anna Malawista Monique M Richards Megan E Cahill Anita Desai Jayasree Sivadasan Manjunatha M Venkataswamy Vasanthapuram Ravi Erol Fikrig Priti Kumar Steven H Kleinstein Smita Krishnaswamy Ruth R Montgomery |
| author_sort |
Yujiao Zhao |
| title |
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. |
| title_short |
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. |
| title_full |
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. |
| title_fullStr |
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. |
| title_full_unstemmed |
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. |
| title_sort |
single cell immune profiling of dengue virus patients reveals intact immune responses to zika virus with enrichment of innate immune signatures. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2020 |
| url |
https://doaj.org/article/b845d9f70c124f9aaf91dca3f01f7623 |
| work_keys_str_mv |
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| _version_ |
1718374127452028928 |