Bidirectional factors impact the migration of NK cells to draining lymph node in aged mice during influenza virus infection

Exp Gerontol. 2017 Oct 1:96:127-137. doi: 10.1016/j.exger.2017.06.021. Epub 2017 Jun 29.

Abstract

Natural killer (NK) cells play an important role in controlling several viral diseases. Our previous studies demonstrated an age-dependent susceptibility to mousepox due to defective NK cell responses and trafficking. However, the mechanisms that underlie the age-related impairment in NK cell migration have yet to be identified. In the present study, we demonstrated that after influenza A virus (IAV) infection, NK cells from aged mice (17-19months old) failed to accumulate in draining lymph node (D-LN). We found that both environmental and intrinsic factors played roles for this defect. After infection, increase of chemokine transcripts, especially CXCL9, 10 and 11, which are important for NK cells homing to D-LN, was significantly lower in the D-LN of aged mice compared with those of young mice. Further, the expression levels of β2-integrins and β-actins, which play critical roles in NK cells homing to D-LN failed to be up-regulated in NK cells from aged mice. Finally, actin polymerization rates in NK cells from aged mice were also delayed compared to that of the young mice after IAV infection. Taken together, our data indicate that bi-directional factors play essential roles in the defective NK cell trafficking to the D-LN in the aged mice after IAV infection.

Keywords: Cell migration; Draining lymph node; IAV infection; Immunosenescence; Infectious disease; NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / metabolism
  • Aging / immunology*
  • Analysis of Variance
  • Animals
  • CD18 Antigens / metabolism
  • Cell Movement / physiology
  • Chemokines / biosynthesis
  • Female
  • Humans
  • Influenza, Human / immunology*
  • Killer Cells, Natural / physiology*
  • Lymph Nodes / physiology*
  • Mice, Inbred C57BL
  • Receptors, Immunologic / metabolism

Substances

  • CD18 Antigens
  • Chemokines
  • Receptors, Immunologic
  • Actinin