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Measles Immune Suppression: Lessons from the Macaque Model
- Source :
- PLoS Pathogens (print), 8(8). Public Library of Science, PLoS Pathogens, PLoS Pathogens, Vol 8, Iss 8, p e1002885 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science, 2012.
-
Abstract
- Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the “measles paradox”. Here we show that MV preferentially infects CD45RA− memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA− memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.<br />Author Summary Measles is associated with a transient immune suppression, resulting in increased susceptibility to opportunistic infections. Indeed, the main causes of measles mortality are secondary infections in the respiratory and digestive tract. Although measles is associated with lymphopenia, depletion of lymphocytes has often been dismissed as a cause of immune suppression. Lymphocyte counts rapidly return to normal after clearance of the virus, while immune suppression lasts several weeks to months. Many studies have focused on suppression of lymphocyte proliferation as an in vitro correlate of immune suppression. However, experimental infections of non-human primates show that in vivo lymphocyte proliferation is not impaired after measles. Instead, we hypothesize that massive expansion of MV-specific and bystander lymphocytes masks the fact that pre-existing memory lymphocytes have been depleted. We conclude that measles virus infection wipes out immunological memory, leaving individuals susceptible to opportunistic infectious agents that would normally be controlled by the immune system.
- Subjects :
- Male
Viral Diseases
T-Lymphocytes
medicine.medical_treatment
Adaptive Immunity
lcsh:QH301-705.5
Lymph node
B-Lymphocytes
0303 health sciences
biology
Immunosuppression
Animal Models
3. Good health
Infectious Diseases
Lymphatic system
medicine.anatomical_structure
Medicine
Female
Macaque
Research Article
lcsh:Immunologic diseases. Allergy
Histology
Lymphoid Tissue
Immune Cells
Green Fluorescent Proteins
Immunology
Antigen-Presenting Cells
Viremia
Immune Suppression
Microbiology
Measles
Lymphocyte Depletion
Measles virus
03 medical and health sciences
Model Organisms
Immune system
SDG 3 - Good Health and Well-being
Virology
Genetics
medicine
Animals
Humans
Antigen-presenting cell
Biology
Immunity to Infections
Molecular Biology
Fluorescent Dyes
030304 developmental biology
Immunosuppression Therapy
030306 microbiology
Immunity
Immune Defense
Leukopenia
medicine.disease
biology.organism_classification
Animal Models of Infection
Disease Models, Animal
lcsh:Biology (General)
Co-Infections
Leukocyte Common Antigens
Macaca
Parasitology
lcsh:RC581-607
Infectious Disease Modeling
Immunologic Memory
Subjects
Details
- ISSN :
- 15537374 and 15537366
- Volume :
- 8
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....cd0875167d4d5968a0288d4ee7e357c8