Polymorphisms in an interferon-gamma receptor-1 gene marker and susceptibility to periodontitis
ACTA ODONTOLOGICA SCANDINAVICA
Authors: Fraser, DA; Loos, BG; Boman, U; van Winkelhoff, AJ; van der Velden, U; Schenck, K; Dembic, Z
Abstract
Chronic marginal periodontitis is an inflammatory condition in which the supporting tissues of the teeth are destroyed. Interferon (IFN)-gamma is a cytokine that plays a pivotal role in the defense against infection, and mutations in the gene coding for the ligand binding chain (alpha, RI) of the IFN-gamma receptor (IFNGRI) confer susceptibility on infections caused by poorly virulent mycobacteria. Using an intronic (CA)(n) polymorphic microsatellite marker within the IFNGRI gene we investigated whether genetic polymorphisms are associated with periodontitis. In 62 periodontitis patients and 56 healthy controls we found a total of 13 polymorphisms, I I of which were found in the periodontitis patients and 9 in the controls. Although we observed a trend towards an association with disease for allele 192, there were no significant differences in allele frequency between patients and controls. We therefore cannot find any evidence to suggest that IFNGRI, as a single dominant gene, contributes to susceptibility to periodontitis. However, in combination with the environmental risk factor, smoking, the same allelic marker was significantly associated [OR = 5.56 (1.16
Development of an in vitro model system to study the interactions between Mycobacterium marinum and teleost neutrophils
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Authors: Hodgkinson, Jordan W.; Ge, Jun-Qing; Katzenback, Barbara A.; Havixbeck, Jeffrey J.; Barreda, Daniel R.; Stafford, James L.; Belosevic, Miodrag
Abstract
The lack of a reliable mammalian neutrophil in vitro culture system has restricted our ability to examine their precise roles in mycobacterial infections. Previously, we developed the procedures for the isolation and culture of primary kidney-derived neutrophil-like cells from goldfish that are functionally and morphologically similar to mammalian neutrophils. The cultured primary goldfish neutrophils exhibited prolonged viability and functional effector responses. In this study, we demonstrate that when exposed to live or heat-killed Mycobacterium marinum, goldfish neutrophils increased their mRNA levels for several pro-inflammatory cytokines (il-1 beta 1, il-1 beta 2, trf alpha-1, tnf alpha-2) and the cytokine receptors (ifngr1-1, trfr1, tnfr2). These neutrophils also exhibited chemotaxis toward live mycobacteria, internalized the bacilli, and produced reactive oxygen intermediates (ROI) in response to pathogen exposure. The survival of intracellular mycobacteria was significantly reduced in activated neutrophils, indicating a robust killing response by these teleost granulocytes. We suggest that this goldfish primary neutrophil in vitro model system will provide important information regarding neutrophil-mediated host defense mechanisms against mycobacteria in teleosts as well as in higher vertebrates. (C) 2015 Elsevier Ltd. All rights reserved.