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Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
- Source :
- PLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e0008112 (2020), PLoS Neglected Tropical Diseases
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- 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.<br />Author summary Mosquitoes carry many globally important human pathogens including a family of related viruses: dengue virus, West Nile virus, Yellow Fever virus, and recently of critical significance, Zika virus. The Zika virus epidemic emerged very rapidly in the susceptible South American population and in many cases immune responses were unable to control the infection. Immune history is a key element of susceptibility or resistance to severe disease. We examined whether pre-existing infection would skew or divert immune resources and might play a role in the severity of Zika infection in the Americas. Using samples from dengue patients and healthy controls from India, we tested functional responses to Zika virus in the context of pre-existing dengue infection. We quantified frequency and functional status of 36 individual cell subsets in depth using advanced profiling techniques and a novel deep learning algorithm. We showed an intact response to new infection with Zika virus which was enriched for early innate immune pathways and robust even during existing dengue infection. Thus, our study suggests that concurrent dengue infection would not be expected to impair immune responses to new infection with Zika virus.
- Subjects :
- RNA viruses
Male
0301 basic medicine
Viral Diseases
Physiology
RC955-962
Dengue virus
Pathology and Laboratory Medicine
medicine.disease_cause
Dengue Fever
Zika virus
Dengue fever
Dengue
White Blood Cells
0302 clinical medicine
Animal Cells
Immune Physiology
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Cytotoxic T cell
Immune Response
Pathogen
Innate Immune System
Immunity, Cellular
T Cells
Zika Virus Infection
Middle Aged
Flow Cytometry
3. Good health
Infectious Diseases
Medical Microbiology
Viral Pathogens
Viruses
Cytokines
Female
Pathogens
Cellular Types
Public aspects of medicine
RA1-1270
Research Article
Neglected Tropical Diseases
Adult
Adolescent
Immune Cells
Immunology
030231 tropical medicine
Cytotoxic T cells
Biology
Microbiology
Young Adult
03 medical and health sciences
Immune system
Immunity
medicine
Humans
Microbial Pathogens
Blood Cells
Innate immune system
Biology and life sciences
Flaviviruses
Organisms
Public Health, Environmental and Occupational Health
Zika Virus
Cell Biology
Dengue Virus
Molecular Development
Tropical Diseases
biology.organism_classification
medicine.disease
Virology
Immunity, Innate
High-Throughput Screening Assays
030104 developmental biology
Immune System
Developmental Biology
Subjects
Details
- ISSN :
- 19352735
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- PLOS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....c57ac89883ca8bbf182b8ee25de43238