TLR4 and major depressive disorder: First, chronic mild stress increases the level of bacterial LPS in the circulation of rats, driving activation of the TLR-4 pathway on blood monocytes (Gárate et al., 2011, 2013), and production of immunoglobulins against LPS is increased in MDD (Maes et al., 2008; Maes and Kubera, 2012; Maes et al., 2013).