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Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity.
PLoS Negl Trop Dis. 2016 Mar; 10(3):e0004497.PN

Abstract

Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.

Authors+Show Affiliations

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Faridabad, Haryana, India.Institute of Genomics and Integrative Biology, New Delhi, India.Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.ICGEB-Emory Vaccine Center, ICGEB campus, New Delhi, India.Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, Faridabad, Haryana, India.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26982706

Citation

Singla, Mohit, et al. "Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes With Disease Severity." PLoS Neglected Tropical Diseases, vol. 10, no. 3, 2016, pp. e0004497.
Singla M, Kar M, Sethi T, et al. Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity. PLoS Negl Trop Dis. 2016;10(3):e0004497.
Singla, M., Kar, M., Sethi, T., Kabra, S. K., Lodha, R., Chandele, A., & Medigeshi, G. R. (2016). Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity. PLoS Neglected Tropical Diseases, 10(3), e0004497. https://doi.org/10.1371/journal.pntd.0004497
Singla M, et al. Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes With Disease Severity. PLoS Negl Trop Dis. 2016;10(3):e0004497. PubMed PMID: 26982706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity. AU - Singla,Mohit, AU - Kar,Meenakshi, AU - Sethi,Tavpritesh, AU - Kabra,Sushil K, AU - Lodha,Rakesh, AU - Chandele,Anmol, AU - Medigeshi,Guruprasad R, Y1 - 2016/03/16/ PY - 2015/09/01/received PY - 2016/02/08/accepted PY - 2016/3/17/entrez PY - 2016/3/18/pubmed PY - 2016/8/3/medline SP - e0004497 EP - e0004497 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 10 IS - 3 N2 - Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/26982706/Immune_Response_to_Dengue_Virus_Infection_in_Pediatric_Patients_in_New_Delhi_India__Association_of_Viremia_Inflammatory_Mediators_and_Monocytes_with_Disease_Severity_ L2 - https://dx.plos.org/10.1371/journal.pntd.0004497 DB - PRIME DP - Unbound Medicine ER -