Serine and cysteine proteases and their inhibitors as antimicrobial agents and immune modulators

Manoury, Bénédicte, Roghanian, Ali and Sallenave, Jean-Michel (2011) Serine and cysteine proteases and their inhibitors as antimicrobial agents and immune modulators. In, Vergnolle, Nathalie and Chignard, Michel (eds.) Proteases and Their Receptors in Inflammation. (Progress in Inflammation Research) Basel, CH. Springer, pp. 27-50. (doi:10.1007/978-3-0348-0157-7_2).

Abstract

Proteases are not merely restricted to digestive purposes and remodeling of extracellular matrix and tissues, but are also key factors for the induction of physiological immune responses. This induction can be direct, through the degradation of pathogens within phagolysosomes, or indirect, through the activation of key pattern recognition receptors (PRRs), such as toll-like receptors (TLRs). Unfortunately, excess production of proteases leads to maladaptive host responses and excess tissue inflammation and damage. Although the mechanisms described here will apply to a variety of different organs, we will deal chiefly with processes occurring in the lung, in pathological conditions such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). To combat these deleterious effects of proteases, the host fortunately produces antiproteases, which directly counteract the proteolytic activities of proteases. In addition to this “straightforward” effect, novel “defensin-like” activities for these molecules are clearly now emerging, as it has recently been demonstrated that protease inhibitors can themselves help in restoring tissue homeostasis by inducing innate and adaptive responses, such as through their interaction with dendritic cells (DCs).

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Contributors

Author: Ali Roghanian

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