| First Author | Pedra JH | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 7 | Pages | 4783-91 |
| PubMed ID | 17878377 | Mgi Jnum | J:152337 |
| Mgi Id | MGI:4358027 | Doi | 10.4049/jimmunol.179.7.4783 |
| Citation | Pedra JH, et al. (2007) ASC/PYCARD and caspase-1 regulate the IL-18/IFN-gamma axis during Anaplasma phagocytophilum infection. J Immunol 179(7):4783-91 |
| abstractText | Anaplasma phagocytophilum is an obligate intracellular pathogen that resides within neutrophils and can cause fever, pancytopenia, or death. IFN-gamma plays a critical role in the control of A. phagocytophilum; however, the mechanisms that regulate IFN-gamma production remain unclear. In this study, we demonstrate that apoptotic specklike protein with a caspase-activating recruiting domain (ASC)/PYCARD, a central adaptor molecule in the Nod-like receptor (NLR) pathway, regulates the IL-18/IFN-gamma axis during A. phagocytophilum infection through its effect on caspase-1. Caspase-1- and asc-null mice were more susceptible than control animals to A. phagocytophilum infection due to the absence of IL-18 secretion and reduced IFN-gamma levels in the peripheral blood. Moreover, caspase-1 and ASC deficiency reduced CD4+ T cell-mediated IFN-gamma after in vitro restimulation with A. phagocytophilum. The NLR family member IPAF/NLRC4, but not NALP3/NLRP3, was partially required for IFN-gamma production in response to A. phagocytophilum. Taken together, our data demonstrate that ASC and caspase-1 are critical for IFN-gamma-mediated control of A. phagocytophilum infection. |
