Location: Food and Feed Safety ResearchTitle: Inhibition of calmodulin increases intracellular survival of Salmonella in chicken macrophage cells Author
|He, Louis - Haiqi|
|Arsenault, Ryan - University Of Delaware|
|Genovese, Kenneth - Ken|
|Swaggerty, Christina - Christi|
|Johnson, Casey - University Of Delaware|
|Nisbet, David - Dave|
|Kogut, Michael - Mike|
Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/4/2019
Publication Date: 5/1/2019
Citation: He, L.H., Arsenault, R.J., Genovese, K.J., Swaggerty, C.L., Johnson, C., Nisbet, D.J., Kogut, M.H. 2019. Inhibition of calmodulin increases intracellular survival of Salmonella in chicken macrophage cells. Veterinary Microbiology. 232:156-161. https://doi.org/10.1016/j.vetmic.2019.02.013.
DOI: https://doi.org/10.1016/j.vetmic.2019.02.013 Interpretive Summary: Salmonella are the most common foodborne pathogens from poultry and are often associated with human salmonellosis. Macrophage cells are white blood cells that can produce chemicals to kill bacteria. Calcium and calcium-binding protein calmodulin are important molecules for maintaining normal function of macrophage cells. In this study, we used a tool called peptide array and a chemical that inhibits calmodulin function to study the role of calmodulin in chicken macrophage cells. Our results show that calmodulin plays a critical role in the immune function of chicken macrophage cells and is needed for chicken macrophage cells to kill Salmonella. Our findings are important to the pharmaceutical and poultry industries in the United States by offering new knowledge to control Salmonella in poultry.
Technical Abstract: Calcium (Ca2+) is a pivotal intracellular second messenger, and calmodulin (CaM) acts as a multifunctional calcium-binding protein that regulates intracellular Ca2+. Together they play an important role in regulating various cellular functions, including gene expression, maturation of phagolysosome, apoptosis, and immune response. Intracellular Ca2+ has been shown to play a critical role in Toll-like receptor-mediated immune response to microbial agonists in chicken macrophage cell line HD11. However, whether the Ca2+/CaM pathway is involved in the intracellular Salmonella survival in chicken macrophages has not been reported. In the present study, a kinome array analysis indicated that Ca2+/CaM pathway was significantly affected when chicken macrophage HD11 cells where infected with S. Enteritidis or S. Heidelberg. Further study demonstrated that treating cells with a pharmaceutical CaM inhibitor W-7, which disrupts the formation of Ca2+/CaM, significantly inhibited macrophages to produce nitric oxide and to control intracellular Salmonella replication. These results strongly indicate that CaM plays an important role in the innate immune response of chicken macrophages and that the Ca2+ / CaM mediated signaling pathway is critically involved in the interaction of Salmonella with the host cells.