Naslov
IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence

Autori
Mandarić, Sanja ; Walton, S. ; Ruelicke, T. ; Richter, K. ; Girard-Madoux, M. ; Clausen, B. ; Zurunić, Antonija ; Kamanaka, M. ; Flavell, R. ; Jonjić, Stipan ; Oxenius, Annette

Izvornik
Plos pathogens (1553-7366) 8 (2012), 8;

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
IL-10; MCMV; NK cells; DCs

Sažetak
IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. Herpes viruses induce IL-10 to modulate the virus-host balance towards their own benefit, resulting in prolonged virus persistence. To define the cellular and molecular players involved in IL-10 modulation of herpes virusspecific immunity, we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10 specifically curtails the MCMV-specific CD4 T cell response by suppressing the bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T cells and we defined the proinflammatory cytokines IL-12, IFN-c and TNF-a as well as NK cell activating receptors NKG2D and NCR-1 to regulate this bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV-specific CD4 T cells in Il102/2 mice led to faster control of lytic viral replication, but this came at the expense of TNF-a mediated immunopathology. Taken together, our data show that early induction of IL-10 during MCMV infection critically regulates the strength of the innateadaptive immune cell crosstalk, thereby impacting beneficially on the ensuing virus-host balance for both the virus and the host.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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