Immune signaling mechanisms of PTSD risk and symptom development: insights from animal models

•Animal models support role for peripheral and central immune signaling in anxiety/fear behavior.•Futures studies must address how specific immune mechanisms contribute to PTSD risk.•Future studies must address the effects of single vs multiple traumas on immune function and anxiety.

Mechanisms underlying posttraumatic stress disorder (PTSD) are not well understood; however, a potential role for immune signaling has recently emerged. Although PTSD is consistently associated with inflammatory markers, a causal role of immune signaling in symptom development is not clear. Here we present the most recent evidence for inflammatory dysfunction both preceding and following PTSD, and current evidence for immune-pathway contributions in animal models of PTSD. We address the role of peripheral vs. central immune signaling, single vs. chronic stress models of PTSD, and use of animal models to investigate novel anti-inflammatory treatments. Gaps in the literature including models of TBI/PTSD comorbidity, peripheral markers of inflammation, and inflammatory trajectories after severe stress are discussed.