| First Author | Lacey CA | Year | 2019 |
| Journal | J Leukoc Biol | Volume | 106 |
| Issue | 1 | Pages | 27-34 |
| PubMed ID | 30748031 | Mgi Jnum | J:276897 |
| Mgi Id | MGI:6315712 | Doi | 10.1002/JLB.4MIA1018-409R |
| Citation | Lacey CA, et al. (2019) IFN-gamma-dependent nitric oxide suppresses Brucella-induced arthritis by inhibition of inflammasome activation. J Leukoc Biol 106(1):27-34 |
| abstractText | Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a globally important zoonotic disease for which arthritis is the most common focal complication in humans. Wild-type mice infected systemically with Brucella typically do not exhibit arthritis, but mice lacking IFN-gamma develop arthritis regardless of the route of Brucella infection. Here, we investigated mechanisms by which IFN-gamma suppresses Brucella-induced arthritis. Several cell types, including innate lymphoid cells, contributed to IFN-gamma production and suppression of joint swelling. IFN-gamma deficiency resulted in elevated joint IL-1beta levels, and severe joint inflammation that was entirely inflammasome dependent, and in particular, reliant on the NLRP3 inflammasome. IFN-gamma was vital for induction of the nitric oxide producing enzyme, iNOS, in infected joints, and nitric oxide directly inhibited IL-1beta production and inflammasome activation in Brucella-infected macrophages in vitro. During in vivo infection, iNOS deficiency resulted in an increase in IL-1beta and inflammation in Brucella-infected joints. Collectively, this data indicate that IFN-gamma prevents arthritis both by limiting Brucella infection, and by inhibiting excessive inflammasome activation through the induction of nitric oxide. |
