Capsule type defines the capability of Klebsiella pneumoniae in evading Kupffer cell capture in the liver

Abstract

Polysaccharide capsule is the main virulence factor ofK.pneumoniae, a major pathogen of bloodstream infections in humans. While more than 80 capsular serotypes have been identified inK.pneumoniae, only several serotypes are frequently identified in invasive infections. It is documented that the capsule enhances bacterial resistance to phagocytosis, antimicrobial peptides and complement deposition underin vitroconditions. However, the precise role of the capsule in the process ofK.pneumoniaebloodstream infections remains to be elucidated. Here we show that the capsule promotesK.pneumoniaesurvival in the bloodstream by protecting bacteria from being captured by liver resident macrophage Kupffer cells (KCs). Our real-timein vivoimaging revealed that blood-borne acapsularK.pneumoniaemutant is rapidly captured and killed by KCs in the liver sinusoids of mice, whereas, to various extents, encapsulated strains bypass the anti-bacterial machinery in a serotype-dependent manner. Using capsule switched strains, we show that certain high-virulence (HV) capsular serotypes completely block KC’s capture, whereas the low-virulence (LV) counterparts confer partial protection against KC’s capture. Moreover, KC’s capture of the LVK.pneumoniaecould bein vivoneutralized by free capsular polysaccharides of homologous but not heterologous serotypes, indicating that KCs specifically recognize the LV capsules. Finally, immunization with inactivatedK.pneumoniaeenables KCs to capture the HVK.pneumoniae. Together, our findings have uncovered that KCs are the major target cells ofK.pneumoniaecapsule to promote bacterial survival and virulence, which can be reversed by vaccination.