Exposure to a Social Stressor Induces Translocation of Commensal Lactobacilli to the Spleen and Priming of the Innate Immune System

Abstract

Studies have shown that exposure to psychological stressors leads to inflammation throughout the body. This has been widely studied using social disruption stress (SDR), a social stressor, which involves repeated social defeat in subordinate mice. Exposure to SDR increases serum cytokine levels, results in accumulation of spleen CD11b+ myeloid cells, and primes macrophages for increased cytokine and microbicidal activity. Our previous studies showed that intestinal microbes are necessary for SDR-enhancement of innate immunity. Here, we show that SDR increases spleen CD11b+Ly6CintermLy6G+ neutrophil and CD11b+Ly6ChiLy6G− monocyte numbers compared to control mice. Further, we found that neutrophils and monocytes from stressor-exposed mice expressed higher levels of IL-1β mRNA. To determine whether bacterial translocation may contribute to these effects, bacterial 16S rRNA was quantified using qRT-PCR with bacterial group-specific primers. Exposure to the SDR stressor specifically increased Lactobacillus RNA in the spleen, which localized in spleen monocytes. The increased spleen levels of Lactobacillus 16S rRNA in SDR mice positively correlated with increased levels of IL-1β and IL-23 mRNA. Our findings indicate that during stressor exposure, Lactobacillus spp. can translocate to the spleen and prime the innate immune system for enhanced reactivity.

Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota

“…Repeated 2-h exposures over 6 days resulted in a greater reduction in Lactobacillus ( Galley et al, 2014a ). Interestingly, reduced Lactobacillus abundance has also been documented in infant monkeys exposed to other forms of psychological stress ( Bailey and Coe, 1999 ; Bailey et al, 2004 ), and recent evidence suggests that translocation of Lactobacillus from the intestinal lumen to the spleen may have the beneficial and adaptive effect of priming stress-induced immune activity ( Lafuse et al, 2017 ). Reduced gut microbiota diversity following exposure to social disruption/defeat, restraint stress, and water avoidance stress has also been reported in several ( Bailey et al, 2010 , 2011 ; Galley et al, 2014b ; Xu D. et al, 2014 ; Bharwani et al, 2016 ), but not all ( Galley et al, 2014a , b , 2017a , b ; Gautam et al, 2018 ) studies.…”

Visceral Inflammation and Immune Activation Stress the Brain

“…Stress exposure not only disrupts the community structure of the gut microbiota ( 253 ) but also induces translocation of, for instance, Lactobacillus spp. to the spleen and primes the innate immune system for enhanced reactivity ( 254 ).…”

Immunosuppressive effect and global dysregulation of blood transcriptome in response to psychosocial stress in vervet monkeys (Chlorocebus sabaeus)

“…Psychosocial stress can also increase the permeability of the intestinal barrier, causing the translocation of bacteria and antigens from the gut to the bloodstream and, in turn, activating pro-inflammatory responses [41][42][43] . To assess the potential effects of PS on the permeability of the gut epithelium and systemic inflammatory state, we investigated plasma levels of the microbial translocation biomarker sCD14, an indicator of monocyte activation, as well as levels of the bacterial endotoxin lipopolysaccharide (LPS).…”