Enhancement of IFN-α and IL-33 production by oral administration
of heat-killed K. pneumoniae
Experimental AIP induced by repeated IP injections of poly (I:C) depends
on the activation of pDCs, which produce large amounts of IFN-α and
IL-33 [14, 16, 19, 20]. Therefore, we examined whether exacerbation
of AIP by orally administered K. pneumoniae was associated with
the activation of pDCs producing both IFN-α and IL-33. We examined
pancreatic immune cell populations by flow cytometry. The percentage of
pDCs defined as PDCA-1+B220low cells
was significantly higher in MRL/MpJ mice that received orally
administered heat-killed K. pneumoniae and IP injections of poly
(I:C) than in those treated with the bacterium or IP injections of poly
(I:C) alone (Fig. 6A, B). In contrast, the combined treatment with
orally administered heat-killed K. pneumoniae and IP injections
of poly (I:C) did not change the percentages of CD11b+myeloid cells, CD11c+ DCs, CD3+ T
cells, or B220+ B cells, as compared with those
following IP injections of poly (I:C) alone (Fig. 6A, B).
Lastly, we determined profiles of proinflammatory cytokine responses in
the pancreas. Consistent with marked accumulation of pDCs,
co-administration of heat-killed K. pneumoniae and poly (I:C)
markedly increased production of IFN-α and IL-33 in the pancreas, as
compared with their levels after the administration of heat-killedK. pneumoniae or poly (I:C) alone (Fig. 7). Pancreatic levels of
the prototypical innate immunity cytokines IL-6 and TNF-α induced by
poly (I:C) injections were similar in the presence and absence of
co-administered heat-killed K. pneumonia. We previously showed
that pancreatic pDCs producing both IFN-α and IL-33 induce pancreatic
expression of adaptive immunity cytokines, including pro-inflammatory
IFN-γ and pro-fibrogenic IL-13 [14, 16, 20]. In line with the
results of those previous studies, co-administration of heat-killedK. pneumoniae and poly (I:C) enhanced pro-inflammatory and
pro-fibrogenic adaptive immune responses because co-administration
markedly elevated pancreatic production of IFN-γ and IL-13, as compared
with the effect of poly (I:C) administration alone (Fig. 7).
Collectively, these data suggest that exacerbation of experimental AIP
by oral administration of heat-killed K. pneumoniae was
accompanied by pancreatic accumulation of pDCs producing IFN-α and
IL-33.