NKT Cell-Plasmacytoid Dendritic Cell Cooperation via OX40 Controls Viral Infection in a Tissue-Specific Manner

Abstract

Invariant natural killer T (iNKT) cells promote immune responses to various pathogens, but exactly how iNKT cells control antiviral responses is unclear. Here, we showed that iNKT cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (LCMV). Indeed, iNKT cells inhibited viral replication in the pancreas and liver but not in the spleen. In the pancreas, iNKT cells expressed the OX40 molecule and promoted type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through OX40-OX40 ligand interaction. Subsequently, this iNKT cell-pDC cooperation attenuated the antiviral adaptive immune response in the pancreas but not in the spleen. The dampening of pancreatic anti-LCMV CD8(+) T cell response prevented tissue damage in transgenic mice expressing LCMV protein in islet beta cells. Thus, this study identifies pDCs as an essential partner of iNKT cells for mounting an efficient, nondeleterious antiviral response in peripheral tissue.

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

“…In contrast to experimental models involving other viruses, [27][28][29][30][31] iNKT cell deficiency did not lead to impaired containment and clearance of DENV in the liver and spleen in our experimental system. This finding is not without precedent because iNKT cells have been shown to be dispensable to control the virus load in some experimental systems.…”

“…Several experimental models have highlighted the beneficial role of iNKT cells in virus-associated inflammatory responses. [27][28][29][30][31][32] However, they can also contribute to the immunopathogenesis of viral diseases. For example, using an experimental mouse model of chronic lung disease triggered by infection with Sendai virus, Kim et al 33 demonstrated that IL-13 production by iNKT cells contributes to pulmonary disease.…”

“…After comparison of the phenotypes of J␣18 Ϫ/Ϫ and wild-type (WT) animals, it was reported that the role of iNKT cells during experimental viral infection can vary according to the virus and experimental conditions. 20,24 -26 For example, during infection with influenza A virus, herpes simplex virus types 1 and 2, and lymphocytic choriomeningitis virus, iNKT cells have a positive role in anti-viral immune responses and virus-associated disease, [27][28][29][30][31][32] whereas during infection with Sendai virus and herpes simplex virus type 2 (only in aged mice), iNKT cells are rather deleterious. 33,34 However, iNKT cells do not seem to participate in anti-viral immunity or control of viral replication during infection with encephalomyocarditis virus and murine cytomegalovirus.…”

NKT cells: Friend or foe during viral infections?

“…2009. 39: 3283-3291 viral load as early as day 1 after viral challenge [44]. This effect was mediated by increased local type 1 IFN release.…”

“…Our own recent study revealed that iNKT cells play a major role in both innate and adaptive anti-LCMV responses in the pancreas, a peripheral tissue. This function of iNKT cells is mediated by local interaction with plasmacytoid DC (pDC), which are key players in innate antiviral responses [44]. These data are further discussed in the section Dichotomous antiviral actions of iNKT cells in lymphoid and non-lymphoid tissues.…”