The endolysosomal cysteine cathepsins L and K are involved in macrophage-mediated clearance of Staphylococcus aureus and the concomitant cytokine induction.
13.09.2013
Müller S, Faulhaber A, Sieber C, Pfeifer D, Hochberg T, Gansz M, Deshmukh SD, Dauth S, Brix K, Saftig P, Peters C, Henneke P, Reinheckel T.
FASEB J. 2014;28(1):162-75
The lysosomal proteases (cathepsins) are known to be present and active in the phagolysosomes of innate immune cells, i.e. macrophages, and are therefore in direct contact with phagocytosed pathogens. However (and a bit surprisingly) the literature has been lacking information whether these proteases are active players in the innate immune response towards bacteria. To address the issue we chose S. aureus-infected primary mouse bone marrow derived macrophages as experimental model. This enabled us to extensively study macrophages from a “battery” of protease deficient mice thereby linking individual proteases to major processes in the macrophage response to bacteria, i.e. phagocytosis and bacterial killing as well as bacteria induced cytokine production, and to delineate at which steps these proteases are active.