Jakubzick, C. V. | Search bioRxiv

bioRxiv2026

Vicarious trauma primes innate immunity and reconfigures human brain networks

Vicarious trauma--witnessing serious harm to others--produces systemic neuroimmune effects in animal models. However, its brain, autonomic, and immune consequences in humans remain unclear. We scanned 88 participants with fMRI during a naturalistic movie-viewing paradigm depicting either industrial cruelty to farm animals (Vicarious Trauma, VT) or positive human-animal interactions (Vicarious Community, VC) with concurrent autonomic physiology and gene expression in circulating monocytes. VT, compared to VC, evoked sustained sympathetic arousal lasting 40 minutes post-viewing and primed innate immune cells to elicit elevated pro-inflammatory (upregulating IL1B and CXCL8) and reduced anti-inflammatory (TGFB1) responses. VT reduced integration in a frontoparietal control system and increased coupling between a salience/action-mode system with paralimbic, basal ganglia, and sensorimotor regions. Disrupted negative coupling between frontoparietal/default-mode and hippocampal systems predicted VT-related CXCL8 increases. These findings shed light on how the brain translates vicarious trauma into the priming of innate immunity.

neuroscience↗

bioRxiv2023

Coordinated Chemokine Expression Defines Macrophage Subsets Across Tissues

Tissue-resident macrophages in the lung comprising alveolar and interstitial macrophages (IMs) display a high degree of heterogeneity. In general, macrophage heterogeneity is thought to arise from various forms of activation that are heavily confounded by the recruitment of monocytes to the tissue-resident macrophage pool. To better understand the functional heterogeneity of IMs in the lung, we profiled the transcription of resident CD206hi and CD206lo IMs under steady-state and inflammatory conditions, excluding recruited macrophages. Rather than observing conventional in vitro M1 and M2 activation states, we identified seven chemokine-expressing IM subsets: IMck1 (Ccl2, Ccl7, Ccl12, and some Cxcl14), IMck2-4 (Ccl3, Ccl4, Ccl5, Cxcl1, Cxcl2, and Cxcl3), IMck5 (Ccl8), IMck6 (Ccl6 and Ccl9), IMck7 (Cxcl9 and Cxcl10), IMck8 (Cxcl13), and IMck9 (Ccl24), which were found in steady-state or induced by acute inflammation. Beyond the mouse lung, similar coordinated chemokine signatures were observed in macrophages and monocytes from other tissues and across species. Although all IMs expressed Pf4 (CXCL4), mainly CD206hi IMs were selectively depleted in Pf4CreR26EYFP-DTR mice. Loss of CD206hi IMs resulted in significantly reduced inflammatory cell influx in allergen- and infection-driven models, as well as significantly diminished tertiary lymphoid formation and subsequent accumulation of GL7+ germinal center B cells. Overall, our study highlights a division of labor among interstitial macrophages, reflected by the coordinated production of chemokines to control inflammatory cell influx and organize tertiary lymphoid tissue architecture. One Sentence SummaryThe study highlights a division of labor among interstitial macrophages, reflected by the coordinated production of chemokines to control inflammatory cell influx and organize tertiary lymphoid tissue architecture.

immunology↗