Table_3_Alterations of the Innate Immune System in Susceptibility and Resilience After Social Defeat Stress.PDF
Dysregulation of innate immune responses has frequently been reported in stress-associated psychiatric disorders such as major depression. In mice, enhanced circulating cytokine levels as well as altered innate immune cell numbers have been found after stress exposure. In addition, stress-induced recruitment of peripheral monocytes to the brain has been shown to promote anxiety-like behavior. However, it is yet unclear whether specific differences in the innate immune system are associated with stress susceptibility or resilience in mice. Utilizing chronic social defeat, a model of depression and stress vulnerability, we characterized peripheral and brain-invading myeloid cells in stress-susceptible and resilient animals. In all defeated animals, we found reduced percentages of CD11c+ dendritic cells (DCs) by flow cytometry in the spleen when compared to non-defeated controls. Exclusively in susceptible mice conventional DCs of the spleen showed up-regulated expression of MHC class II and co-stimulatory CD80 molecules pointing toward an enhanced maturation phenotype of these cells. Susceptible, but not resilient animals further exhibited an increase in inflammatory Ly6Chi monocytes and higher numbers of spleen-derived CD11b+ cells that produced the proinflammatory cytokine tumor necrosis factor (TNF) upon lipopolysaccharide (LPS) stimulation. Increased percentages of peripheral CD45hi CD11b+ cells immigrated into the brain of defeated mice, regardless of resilience or susceptibility. However, cellular infiltrates in the brain of susceptible mice contained higher percentages of CC chemokine receptor 2 (CCR2+) Ly6Chi monocytes representing an inflammatory phenotype. Thus, we defined specific stress-related immune signatures involving conventional DCs and inflammatory Ly6Chi monocytes in susceptible and resilient mice. Together, our findings suggest an impact of the innate immune system in vulnerability to stress-related disorders such as major depression.
History
References
- https://doi.org//10.1016/s0899-9007(02)00854-7
- https://doi.org//10.1016/j.bbr.2016.07.041
- https://doi.org//10.1371/journal.pone.0081744
- https://doi.org//10.2174/1381612053381684
- https://doi.org//10.1126/science.1120972
- https://doi.org//10.1016/j.biopsych.2012.09.021
- https://doi.org//10.1523/JNEUROSCI.2278-14.2015
- https://doi.org//10.1523/JNEUROSCI.3177-10.2010
- https://doi.org//10.1016/j.pharmthera.2011.01.014
- https://doi.org//10.1016/j.psychres.2010.10.029
- https://doi.org//10.1186/s12868-015-0169-z
- https://doi.org//10.1016/j.bbi.2012.12.017
- https://doi.org//10.1186/s12974-016-0572-0
- https://doi.org//10.1038/nrn2297
- https://doi.org//10.1016/j.clindermatol.2011.11.003
- https://doi.org//10.1097/00062752-200101000-00009
- https://doi.org//10.1016/j.biopsych.2009.09.033
- https://doi.org//10.1016/j.jneuroim.2003.11.011
- https://doi.org//10.1016/j.jneuroim.2004.08.005
- https://doi.org//10.1038/npp.2016.125
- https://doi.org//10.1038/s41598-017-15897-2
- https://doi.org//10.1016/j.bbi.2017.10.025
- https://doi.org//10.1073/pnas.1202208109
- https://doi.org//10.1038/nri1733
- https://doi.org//10.1038/nri2550
- https://doi.org//10.1016/j.physbeh.2005.02.011
- https://doi.org//10.1016/j.bbi.2015.12.003
- https://doi.org//10.1038/nm.3589
- https://doi.org//10.1073/pnas.1415191111
- https://doi.org//10.1159/000343100
- https://doi.org//10.1016/j.neuropharm.2011.08.018
- https://doi.org//10.1001/archpsyc.62.6.593
- https://doi.org//10.1159/000331586
- https://doi.org//10.1016/j.physbeh.2007.11.003
- https://doi.org//10.1002/wsbm.32
- https://doi.org//10.1111/acps.12698
- https://doi.org//10.1016/j.cell.2007.09.018
- https://doi.org//10.1038/nature07455
- https://doi.org//10.4049/jimmunol.1601269
- https://doi.org//10.1016/j.bbi.2016.12.019
- https://doi.org//10.1186/s12974-016-0672-x
- https://doi.org//10.1684/ecn.2015.0362
- https://doi.org//10.1016/0022-3956(92)90004-8
- https://doi.org//10.1038/s41593-017-0010-3
- https://doi.org//10.1073/pnas.1114153109
- https://doi.org//10.1016/j.bbi.2008.09.010
- https://doi.org//10.1016/j.bbi.2010.07.243
- https://doi.org//10.1002/glia.20467
- https://doi.org//10.1007/7854_2016_25
- https://doi.org//10.1038/nature09615
- https://doi.org//10.1016/j.neuroscience.2015.01.001
- https://doi.org//10.1073/pnas.1600324113
- https://doi.org//10.1016/s0006-8993(99)02189-7
- https://doi.org//10.1016/j.bbi.2017.06.010
- https://doi.org//10.3390/ijms18112306
- https://doi.org//10.3389/fnbeh.2017.00207
- https://doi.org//10.1146/annurev-immunol-100311-102839
- https://doi.org//10.4049/jimmunol.1601463
- https://doi.org//10.1016/j.immuni.2011.10.014
- https://doi.org//10.1146/annurev.iy.13.040195.001343
- https://doi.org//10.1523/JNEUROSCI.1787-13.2014
- https://doi.org//10.1371/journal.pone.0058488
- https://doi.org//10.1016/s1359-6101(03)00043-1
- https://doi.org//10.1016/j.pnpbp.2016.04.013
- https://doi.org//10.1523/JNEUROSCI.0450-11.2011
- https://doi.org//10.1523/JNEUROSCI.1671-13.2013
- https://doi.org//10.1017/neu.2015.36
- https://doi.org//10.1038/srep19406