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.
Highlights
To detect and lyse target cells, Natural killer (NK) cells use distinct mechanisms: Antibody-dependent cell-mediated cytotoxicity (ADCC) and natural cytotoxic activity[7]
Since both dendritic cells (DCs) and NK cells serve as essential part of a crucial “first line of defence” and are among the initial immune cells encountered by chlamydia during infection[1], we asked whether NK cells are capable of being infected by the bacteria and whether they mount self-defence strategies against such infections
By using KY-2 cells[31] and the non-avian C. psittaci strain DC1532 as a suitable model system for chlamydial infection, we first investigated whether and by what cellular uptake mechanism KY-2 cells are infected with chlamydia
Summary
To detect and lyse target cells, NK cells use distinct mechanisms: Antibody-dependent cell-mediated cytotoxicity (ADCC) and natural cytotoxic activity[7]. NK cells are among the first cells at the chlamydial infection site, as early as ≤24 hours post infection (hpi), and play an important role in the initial control of the immune response[22] They are stimulated to secrete IFN-γ by infected DCs and epithelial cells, which produce IL-12 and IL-18, respectively[23]. We had demonstrated that C. psittaci-infected DCs harbour cell-autonomous self-protection mechanisms that disintegrate chlamydial inclusions and routes them for xenophagic degradation, leading to the generation of MHC I presented antigens[30] Since both DCs and NK cells serve as essential part of a crucial “first line of defence” and are among the initial immune cells encountered by chlamydia during infection[1], we asked whether NK cells are capable of being infected by the bacteria and whether they mount self-defence strategies against such infections. Unravelling the interaction between NK cells and chlamydia will help to better understand the initial defence strategies and molecular key mechanisms during the innate immune response against bacterial pathogens
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