As many bacterial pathogens use type III secretion systems to deliver effector proteins into host cells, the authors examined the function of BopN during B. bronchiseptica infection. Dendritic cells infected in vitro with bacteria lacking BopN (ΔbopN) had reduced Il10 mRNA levels compared with cells infected with wild-type bacteria. Consistent with this, mice infected with ΔbopN bacteria produced significantly lower levels of IL-10 and higher levels of the pro-inflammatory cytokine interferon-γ (which is suppressed by IL-10) and had higher survival rates than mice infected with wild-type bacteria. These findings indicate an integral role for BopN in mediating IL-10 production and promoting bacterial survival.
So how does B. bronchiseptica increase IL-10 production? Mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways are known to be modulated during B. bronchiseptica infection and to affect the expression of cytokines, including IL-10. Indeed, introduction of BopN into a cell line triggered MAPK dephosphorylation, which coincided with increased Il10 mRNA levels. Moreover, BopN translocated to the nucleus and altered the localization of the NF-κB subunits p50 and p65. Specifically, BopN enhanced the nuclear translocation of p50 (which is known to upregulate IL-10) and blocked that of p65. These changes in NF-κB localization could be the mechanism by which BopN increases IL-10 production. Treatment of dendritic cells with an inhibitor of nuclear export reduced IL-10 production in cells infected with wild-type bacteria, but ΔbopN-infected cells did not produce IL-10 in the presence or absence of the inhibitor.
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