Protective Role of Kupffer Cells and Macrophages in Klebsiella pneumoniae-Induced Liver Abscess Disease

Abstract

Klebsiella pneumoniae-induced liver abscess (KLA) is emerging as a leading cause of pyogenic liver abscess worldwide. In recent years, the emergence of hypervirulent K. pneumoniae (hvKp) has been strongly associated with KLA. Unlike classical K. pneumoniae, which generally infects the immunocompromised population, hvKp can cause serious and invasive infections in young and healthy individuals. hvKp isolates are often associated with the K1/K2 capsular types and possess hypermucoviscous capsules. KLA is believed to be caused by K. pneumoniae colonizing the gastrointestinal tract of the host and translocating across the intestinal barrier via the hepatic portal vein into the liver to cause liver abscess. We optimized the isolation of the liver-resident macrophages called Kupffer cells in mice and examined their importance in controlling bacterial loads during hvKp infection in healthy mice. Our study reveals the high capability of Kupffer cells to kill hvKp in vitro despite the presence of the bacterial hypermucoviscous capsule, in contrast to other macrophages, which were unable to phagocytose the bacteria efficiently. Depletion of Kupffer cells and macrophages with liposome-encapsulated clodronate (liposomal clodronate) in both an intraperitoneal and an oral mouse infection model resulted in increased bacterial loads in the livers, spleens, and lungs and increased mortality of the infected mice. Thus, Kupffer cells and macrophages are critical for the control of hvKp infection.

The hypermucoviscosity of hypervirulent K. pneumoniae confers the ability to evade neutrophil-mediated phagocytosis

“…Consistently, NP-HvKP/A and NP-HvKP/A2 exhibited reduced ability to adhere to the epithelial cells ( Figure 2(c,d )) or undergo phagocytosis by macrophage ( Figure 2(e )), as well as a lower chance of being killed by neutrophils ( Figure 3(b )). Our data is consistent with previous reports that HvKP exhibited lower phagocytosis by macrophage when compared to cKP strains [ 18 , 28 ]. However, another study reported that deletion of rmpA ( ∆rmpA ) in a HvKP strain, SGH10, exhibited no effect on uptake by RAW264.7 macrophages as well as adhesion to Caco-2 cells [ 18 ].…”

Deoxycholic Acid and Lithocholic Acid Alleviate Liver Injury and Inflammation in Mice with Klebsiella pneumoniae-Induced Liver Abscess and Bacteremia

“…These results suggested that liver abscesses cause a certain degree of immune inflammation. 44 An increase in ALT and AST, two sensitive markers indicating liver injury, was detected in K. pneumoniae -infected mice. It is worth mentioning that the levels of p-IκBα, nuclear NF-κB p65, and p50 subunits in the liver were significantly increased, suggesting the activation of the NF-κB pathway.…”

“…However, we found that it was reported the absolute numbers of Kupffer cells were quite constant except for a small increase during the 12h and 24h time points. 44 Different results may be related to different modeling methods, observation time points and experimental techniques. The current study also found that macrophagic infiltration promotes the rapid release of TNF-α, MCP-1, KC, and IP-10, amplifying the inflammatory cascade, finally leading to inflammatory storms.…”

Liver Abscess and Septic Pulmonary Dissemination by Klebsiella pneumoniae in a Hispanic Male: A Case Report

“…characterized by a monomicrobial pyogenic liver abscess with or without extrahepatic seeding in the absence of previous biliary disease, intra-abdominal infection or recent intra-abdominal surgery [9,10]. The pathogen's source is generally the gastrointestinal tract and is acquired through fecal-oral transmission [11,12].…”

“…The pathogen's source is generally the gastrointestinal tract and is acquired through fecal-oral transmission [11,12]. After colonization, enteric bacteria are believed to translocate through the portal venous circulation [10] into the liver. Intestinal colonization may serve as a reservoir for pathogenic strains although evidence can be discordant [13,14] (Figure 3).…”