Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections

The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6...

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Bibliographic Details
Published in:PloS one 2016-08, Vol.11 (8), p.e0161795-e0161795
Main Authors: Toro, Jessica F, Salgado, Doris M, Vega, Rocío, Rodríguez, Jairo A, Rodríguez, Luz-Stella, Angel, Juana, Franco, Manuel A, Greenberg, Harry B, Narváez, Carlos F
Format: Article
Language:English
Subjects:
Adolescent
Age
Age Factors
Antibodies, Viral - blood
Antibodies, Viral - immunology
Antibody-Producing Cells - immunology
Antibody-Producing Cells - virology
B cells
B-Lymphocyte Subsets - immunology
B-Lymphocyte Subsets - virology
Biology and Life Sciences
Child
Child, Preschool
Children
Chronology
Comparative analysis
Cross Reactions - immunology
Cytokines
Dengue
Dengue - blood
Dengue - immunology
Dengue - virology
Dengue fever
Dengue Virus - genetics
Dengue Virus - immunology
Dengue Virus - physiology
Development and progression
Enzyme-Linked Immunospot Assay
Female
Genetic aspects
Hospitals
Host-Pathogen Interactions - immunology
Humans
Immune status
Immunoglobulin G
Immunoglobulin G - blood
Immunoglobulin G - immunology
Immunoglobulin M
Immunoglobulin M - blood
Immunoglobulin M - immunology
Immunoglobulins
Infant
Infants
Infections
Lymphocytes B
Male
Medicine and Health Sciences
Pediatrics
People and Places
Physiological aspects
Plasma
Production capacity
Proteins
Research and Analysis Methods
Secondary infection
Serogroup
Serotypes
Tumor necrosis factor-TNF
Vector-borne diseases
Viral envelope proteins
Viral Envelope Proteins - immunology
Viral infections
Virology
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Summary:The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6-12 months old) and children (1-14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = -0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0161795