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Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus


Type I interferons (IFN-I) are innate cytokines crucial for vertebrate antiviral defenses. IFN-I exert antiviral effector functions and orchestrate antiviral immunity. IFN-I are induced early after infection, upon sensing of viral particles or infected cells by immune receptors. Intracellular Toll-like receptors (TLR) are selectively expressed in specialized immune cell types such as plasmacytoid dendritic cells (pDC), enabling them to copiously produce IFN-I upon detection of engulfed viral nucleic acids. pDC or intracellular TLR have been reported to be crucial for resistance to experimental infections with many viruses in mice but dispensable for resistance to natural infections in humans. Our aim was to investigate this puzzling difference. Mice deficient for TLR activity mounted strong IFN-I responses despite producing very low IFN-I levels and controlled the infection by a moderate dose of murine cytomegalovirus much better than mice deficient for IFN-I responses. Deficient TLR responses could be compensated by direct recognition of infected cells by natural killer cells. Hence, we identified experimental conditions in mice mimicking the lack of requirement of TLR functions for antiviral defense observed in humans. We used these experimental models to advance our basic understanding of antiviral immunity in a way that might help improve treatments for patients.


Vyšlo v časopise: Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004897
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004897

Souhrn

Type I interferons (IFN-I) are innate cytokines crucial for vertebrate antiviral defenses. IFN-I exert antiviral effector functions and orchestrate antiviral immunity. IFN-I are induced early after infection, upon sensing of viral particles or infected cells by immune receptors. Intracellular Toll-like receptors (TLR) are selectively expressed in specialized immune cell types such as plasmacytoid dendritic cells (pDC), enabling them to copiously produce IFN-I upon detection of engulfed viral nucleic acids. pDC or intracellular TLR have been reported to be crucial for resistance to experimental infections with many viruses in mice but dispensable for resistance to natural infections in humans. Our aim was to investigate this puzzling difference. Mice deficient for TLR activity mounted strong IFN-I responses despite producing very low IFN-I levels and controlled the infection by a moderate dose of murine cytomegalovirus much better than mice deficient for IFN-I responses. Deficient TLR responses could be compensated by direct recognition of infected cells by natural killer cells. Hence, we identified experimental conditions in mice mimicking the lack of requirement of TLR functions for antiviral defense observed in humans. We used these experimental models to advance our basic understanding of antiviral immunity in a way that might help improve treatments for patients.


Zdroje

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