Immune response and pathophysiological features of Klebsiella pneumoniae liver abscesses in an animal model

Abstract

Capsular serotypes K1 and K2, the rmpA gene (a regulator of the mucoid phenotype) and aerobactin from Klebsiella pneumoniae have been identified as the major virulence factors for pyogenic liver abscesses with high morbidity, mortality and severe complications. The pathological mechanisms remain unclear. In this study, we compared liver immune responses and pathological changes in response to different serotypes of K. pneumoniae infections. A mouse model was used to investigate cytokine and chemokine production, histopathology findings, phagocytic uptake and mortality induced by serotypespneumoniae serotypes K1 and K2 showed lower 50% lethal dose values and more phagocytic resistance to neutrophils than K62 and the DK1 mutant. In sequential liver samples, viable bacteria counts increased 3 h to 3 days after low-dose inoculation (o10 1 colony-forming unit (cfu)) with K1 and K2, while K62 and DK1 cleared rapidly and became undetectable even with high-dose inoculation (B2.9 Â 10 5 cfu). Time-dependent increases in cytokines and chemokines, including tumor necrosis factor-a, interleukin (IL)-1b, IL-6, IL-10, keratinocyte-derived chemokines and macrophage inflammatory protein-2, were observed in the serum and liver tissue of K1-and K2-infected mice, and severe disease progression manifesting as microabscesses was also identified. K62 and DK1 inoculation did not result in similar immune responses and histological changes. These findings illustrate the critical role of phagocytic resistance against innate immunological defense mechanisms as well as its contribution to the development of liver abscesses.

Resistance of Klebsiella pneumoniae to the innate immune system of African green monkeys

“…In mice, magA + /rmpA + and magA À /rmpA + K. pneumoniae isolates were found to be significantly more virulent than magA À , rmpA À , and an unencapsulated isogenic K1 mutant (DK1, magA + , rmpA + ) isolate (Fung et al, 2011). magA + / rmpA + and magA À /rmpA + K. pneumoniae were significantly more invasive and virulent in vivo, and presented significantly different cytokine and chemokine responses than magA À /rmpA À isolates (Fung et al, 2011).…”

“…The HMV phenotype of K. pneumoniae has been associated with the presence of virulence genes, magA and rmpA, and with serotypes K1, K2 and K5. The importance of the K antigen, magA and rmpA and HMV phenotype in K. pneumoniae virulence has been shown in a mouse model (Simoons-Smit et al, 1986;Lin et al, 2011;Fung et al, 2011), but as in vivo challenges have not been conducted in AGM, a direct comparison between species is not possible.…”

“…In humans, serotypes K1-K6 are associated more frequently with severe respiratory infection and septicemia than the higher numbered serotypes (Simoons-Smit et al, 1986;Fung et al, 2011). In equine hosts, serotypes K2, K5, and K7 are considered the most pathogenic (Crouch et al, 1972).…”

TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice

“…K. pneumoniae strain STL43 (capsular type K1) was isolated from a patient with liver abscesses, as described previously (32), and was used for all experiments involving the oral infection model of liver abscess. The NTUH-K2044 (capsular type K1) strain with a green fluorescent protein (GFP)-expressing plasmid, which conferred kanamycin resistance, was used for the translocation assay.…”

Liver Abscesses as Pseudotumoral Lesions

“…The pathogenic mechanism by which this distinct Klebsiella phenotype is related to the unique clinical presentation is only partially known. Expression of K1 antigen hampers complement-and neutrophilmediated killing of Klebsiella, a mechanism thought to promote an invasive phenotype Fung et al 2011). In fact, capsular serotypes K 1 and K2 impair Klebsiella phagocytosis in type 2 diabetic patients , and phagocytosis-resistant Klebsiella serotypes are highly prevalent in PLA (Lin et al 2004).…”