Project 1

Immunoregulatory approaches to promote stress resistance.

It is the major aim of this Project, in collaboration with the lab of Prof. Dr. Christopher Lowry (University of Colorado, Boulder, USA), to promote resilience against stress-related somatic and affective pathologies by treating mice either prior to or following/during stress/psychosocial trauma exposure with a heat-killed preparation of immunoregulatory "old friends from mud and soil", including Mycobacterium vaccae (NCTC 11659; Fig. 3 left panel; taken from Reber et al., 2016 PNAS Figure S2A), and to reveal the underlying mechanisms. Our mouse data so far support a strategy of "re-introducing" humans to their "old friends" in order to promote optimal health and stress/trauma resilience. In detail, this is based on the fact that M. vaccae pre-immunization causes a shift from passive towards active stress coping during CSC exposure, has anxiolytic effects, and prevents development of spontaneous and aggravation of chemically-induced colitis (Reber et al., 2016 PNAS). Effects on anxiety and colitis, but not on "stress coping", were mediated via Treg cell induction. Consistent with the finding, that Treg cells and IL-10 secretion play an important role in the stress/trauma-protective effects of M. vaccae, CSC-induced promotion of a colitogenic gut micromilieu was not corrected by pre-immunization with this "old friends" (Fig. 3 right panel; taken from 2016 PNAS Figure S6M).

We are currently investigating whether i) p.o. or i.n. application of M. vaccae is stress protective as well, ii) M. vaccae immunization is able to treat already existing stress-related disorders, iii) other "old friends" have a comparable potential to prevent stress-associated disorders.

Funding: Office of Naval Research Global, N00014-17-S-B001; Grant12274897 (M. vaccae) & university intern budget (other "old friends")