A Janus role for MerTK in the outcome of septic shock

Excerpt

Severe sepsis remains a clinical challenge today, even in developed countries, because of the increased age of the patients and the high burden of antibiotic resistance [1]. In addition, in recent years, we have become increasingly aware that, even in the early stages of sepsis, a high proportion of patients experience a severe dysfunction of native and adaptive immunity, which is closely related to patients’ outcome [2]. In this context, understanding the functionality of receptors able to modulate the immune response, and in particular to downregulate inflammation, has great importance for designing new therapeutic strategies. Among these molecules, a main role is occupied by the TAM family of receptor tyrosine kinases, which is formed by three members, i.e., Tyro3, AxI, and Mer, that have two vitamin K-dependent ligands, i.e., the growth arrest-specific protein (Gas)6 and Protein S [3]. In the September 2013 issue of Intensive Care Medicine, Guignant et al. [4] explored by an elegant experimental study the expression of TAM receptors in circulating immune cells in patients with septic shock and after trauma, and in healthy volunteers. A significant early alteration of MerTK expression on monocytes and neutrophils was observed in patients with septic shock, and a persistent MerTK overexpression after septic shock was associated with adverse outcome. The ex vivo analysis showed also a different MerTK surface expression of healthy monocytes after 48 h incubation with plasma from septic or trauma patients, supporting the difference in TAM expression between infection-induced inflammation and sterile inflammation (i.e., trauma). The study provides new important data on the mechanisms of immune response in sepsis, but the true reasons for the observed alterations in MerKT expression and their role in the complex pathophysiological context of sepsis remain to be clarified. …