European Journal of Immunology
European Journal of Immunology
5 years ago

NCR1-deficiency diminishes the generation of protective murine cytomegalovirus antibodies by limiting follicular helper T-cell maturation

NCR1-deficiency diminishes the generation of protective murine cytomegalovirus antibodies by limiting follicular helper T-cell maturation
Astrid Krmpotic, Antonija Miletic, Karmela Miklic, Tihana Trsan, Maja Lenartic, Stipan Jonjic, Branka Popovic, Ofer Mandelboim, Ilija Brizic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1gfp/gfp) mice, we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4+ T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation. As a consequence, NCR1gfp/gfp mice produced lower amounts of MCMV-specific antibodies upon infection, which correlated with lower number of virus-specific antibody secreting cells in analyzed lymph nodes. NCR1-deficient mice showed lower activation of cDCs and impaired CXCR3-dependant migration of NK cells to regional lymph nodes. This resulted in diminished formation of follicular helper CD4+ T cells leading to inferior induction of humoral response and lower production of high-affinity virus-specific antibodies in comparison to wild-type mice.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201646763

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