NK Cell-Mediated Processing Of Chlamydia psittaci Drives Potent Anti-Bacterial Th1 Immunity

Sci Rep. 2019 Mar 18;9(1):4799. doi: 10.1038/s41598-019-41264-4.

Abstract

Natural killer (NK) cells are innate immune cells critically involved in the early immune response against various pathogens including chlamydia. Here, we demonstrate that chlamydia-infected NK cells prevent the intracellular establishment and growth of the bacteria. Upon infection, they display functional maturation characterized by enhanced IFN-γ secretion, CD146 induction, PKCϴ activation, and granule secretion. Eventually, chlamydia are released in a non-infectious, highly immunogenic form driving a potent Th1 immune response. Further, anti-chlamydial antibodies generated during immunization neutralize the infection of epithelial cells. The release of chlamydia from NK cells requires PKCϴ function and active degranulation, while granule-associated granzyme B drives the loss of chlamydial infectivity. Cellular infection and bacterial release can be undergone repeatedly and do not affect NK cell function. Strikingly, NK cells passing through such an infection cycle significantly improve their cytotoxicity. Thus, NK cells not only protect themselves against productive chlamydial infections but also actively trigger potent anti-bacterial responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD146 Antigen / metabolism
  • Cell Communication / immunology
  • Cells, Cultured
  • Chlamydophila psittaci / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunity, Cellular*
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / microbiology
  • Mice
  • Primary Cell Culture
  • Protein Kinase C-theta / metabolism
  • Psittacosis / blood
  • Psittacosis / immunology*
  • Psittacosis / microbiology
  • Spleen / cytology
  • Th1 Cells / immunology*

Substances

  • CD146 Antigen
  • IFNG protein, mouse
  • Mcam protein, mouse
  • Interferon-gamma
  • Protein Kinase C-theta