Pathogenicity of heat-killed K. pneumoniae in experimental AIP
The association between reduced colonization by Klebsiella spp.and induction of remission led us to examine the pathogenicity of this bacterium in AIP. Therefore, we employed a well-established murine model of AIP in MRL/MpJ mice [14, 16, 19, 20]. Repeated IP injections of poly (I:C) into MRL/MpJ mice at a higher dose of 100 µg triggered severe AIP, characterized by massive infiltration of immune cells, destruction of acinar architecture, and fibrosis; whereas, repeated IP injections at a lower dose of 10 µg caused mild AIP with infiltration of immune cells [14, 16, 19, 20]. We hypothesized that immune responses againstKlebsiella spp. increase the sensitivity to experimental AIP. To test this hypothesis, MRL/MpJ mice received combined treatment with orally administered heat-killed K. pneumoniae and IP injections of poly (I:C) (10 µg) twice a week, for a total of 16 times.
As expected, infiltration of immune cells was seen in the pancreas of MRL/MpJ mice that received IP injections of 10 µg of poly (I:C) alone (Fig. 5A). Interestingly, this infiltration was accompanied by the destruction of acinar architecture in the pancreas of MRL/MpJ mice following combined treatment with orally administered heat-killedK. pneumoniae and IP injections of poly (I:C) (Fig. 5A). Quantitative assessment of pathological scores confirmed that oral administration of heat-killed K. pneumoniae promoted the development of pancreatitis (Fig. 5B).