A detrimental role for invariant natural killer T cells in the pathogenesis of experimental Dengue virus infection

Renneson, J. et al. (2011) A detrimental role for invariant natural killer T cells in the pathogenesis of experimental Dengue virus infection. American Journal of Pathology, 179(4), pp. 1872-1883. (doi: 10.1016/j.ajpath.2011.06.023)

Abstract

Dengue virus (DENY), a member of the mosquito-borne flaviviruses, is a serious public health problem in many tropical countries. We assessed the in vivo physiologic contribution of invariant natural killer T (iNKT) cells, a population of nonconventional lipid-reactive alpha beta T lymphocytes, to the host response during experimental DENY infection. We used a mouse-adapted DENY serotype 2 strain that causes a disease that resembles severe dengue in humans. On DENY challenge, splenic and hepatic iNKT cells became activated insofar as CD69 and Fas ligand up-regulation and interferon-gamma production. C57BL/6 mice deficient in iNKT cells (J alpha 18(-/-)) were more resistant to lethal infection than were wild-type animals, and the phenotype was reversed by adoptive transfer of iNKT cells to J alpha 18(-/-) animals. The absence of iNKT cells in J alpha 18(-/-) mice was associated with decreased systemic and local inflammatory responses, less liver injury, diminished vascular leak syndrome, and reduced activation of natural killer cells and neutrophils. iNKT cell functions were not necessary for control of primary DENY infection, after either natural endogenous activation or exogenous activation with the canonical iNKT cell agonist alpha-galactosylceramide. Together, these data reveal a novel and critical role for iNKT cells in the pathogenesis of severe experimental dengue disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Guabiraba Brito, Dr Rodrigo
• Authors: Renneson, J., Guabiraba Brito, R., Maillet, I., Marques, R.E., Ivanov, S., Fontaine, J., Paget, C., Quesniaux, V., Faveeuw, C., Ryffel, B., Teixeira, M.M., and Trottein, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: American Journal of Pathology
• ISSN: 0002-9440
• ISSN (Online): 0002-9440