How Natural Killer Cells Conquer Klebsiella

The inappropriate or excessive use of antimicrobial agents in past decades has propelled the emergence and spread of multidrug resistant microbial pathogens. According to the European Centre for Disease Prevention and Control and the European Medicines Agency, each year about 25.000 patients in the EU die from infections with multidrug-resistant bacteria. Globally, 700,000 people per year die due to antimicrobial resistance.

Earlier this year, the World Health Organization (WHO) published a report on anti-microbial resistance, with a special emphasis on antibiotic resistance of so-called superbugs. Such bacteria pose the greatest threat to human health due to their resistance to several different antibiotics.  Among these superbugs is Klebsiella, which can cause severe and often fatal infections of the bloodstream and lungs. Klebsiella has been reported to be resistant to common classes of antibiotics and to a great extent also to carbapenems, the last resort to treat severe nosocomial infections.

The researchers in the labs of Pavel Kovarik at MFPL and Jose Bengoechea at Queen’s University Belfast now discovered how immune cells arriving at the site of infection communicate and join forces to eradicate Klebsiella during lung infections. Their study suggests that future therapies of severe Klebsiella infections could target the immune system, rather than the pathogen itself.

The scientists report the mechanism of how natural killer cells, important cells of the innate immune system, control the growth of Klebsiella during lung infection. Klebsiella induces critical immune response regulators, type I interferons (IFNs), which act as middlemen in the crosstalk between alveolar macrophages (immune cells that engulf and "eat" microbes) and natural killer cells. Type I IFNs help activate natural killer cells, which in turn license macrophages to launch an antibacterial program. "Type I IFNs are used by the immune system to transport messages between immune cells to orchestrate a perfect defense. Natural killer cells represent the conductor of the defense orchestra, whereas macrophages are the bacteria-killing instruments," explains Masa Ivin, first author of the study and PhD student in the Kovarik lab at the MFPL.

Future perspectives Pavel Kovarik and his team are optimistic that their new found results will contribute to the development of urgently needed novel therapeutics against multidrug resistant pathogens. "If drugs fail to kill the pathogen, we should help the immune system do the job. Our current study identifies new and feasible ways how to support the immune system in fighting superbugs."

The research was supported by the Marie Curie Initial Training Network INBIONET, a part of the EU’s Seventh Framework Programme, and the Austrian Research Fund FWF.

Publication in PLOS Pathogens Masa Ivin, Amy Dumigan, Filipe N. de Vasconcelos, Florian Ebner, Martina Borroni, Anoop Kavirayani, Kornelia N. Przybyszewska, Rebecca J. Ingram, Stefan Lienenklaus, Ulrich Kalinke, Dagmar Stoiber, Jose A. Bengoechea and Pavel Kovarik: Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection. PLOS Pathogens. https://doi.org/10.1371/journal.ppat.1006696

Source: University of Vienna