Sleep Deprivation Induces Changes in Immunity in Trichinella spiralis-Infected Rats

Abstract

Sleep is considered an important predictor of immunity. A lack of sleep may reduce immunity, which increases susceptibility to any type of infection. Moreover, sleep deprivation in humans produces changes in both, the percent of circulating immune cells (T cells and NK cells) and cytokine levels (IL-1, IFNγ, TNΦ-αα, IL-6 and IL-17). The aim of our study was to investigate whether sleep deprivation produces deregulation on immune variables during the immune response generated against the helminth parasite Trichinella spiralis. Because sleep deprivation is stressful per se, we designed another experiments to compared stress alone (consisting in movement restriction and single housing) with sleep deprivation, in both control (uninfected) and experimental (infected) rats. Our results demonstrate that the sleep deprivation and stress have a differential effect in mesenteric lymph nodes (MLN) and spleen. In uninfected rats sleep deprivation alone produces an increase in natural killer cells (NK+) and B cells (CD45+), accompanied by a decrease in cytotoxic T cells (CD3+CD8+) in spleen; while, in MLN, produces only an increase in natural killer cells (NK+). Both, SD and stress, produce an increased percentage of total T cells (CD3+) in spleen. In the MLN both are also associated to an increase in cytotoxic T cells (CD3+CD8+) and B cells (CD45+). In the spleens of parasitized rats, cell populations did not change. In spleens of both, sleep-deprived and stressed infected rats, we observed an increase in B cells (CD45+). In infected rats, sleep deprivation alone produced an increase in NK cells (NK+). In mesenteric node cell populations of parasitized rats, we observed a decrease in NK cells and an increase in T helper (CD4+) cells in both SD and stressed rats. Rats that were only subjected to stress showed a decrease in B cells (CD45+). These findings suggest that the immune response generated against infection caused by T. spiralis is affected when the sleep pattern is disrupted. These results support the notion that sleep is a fundamental process for an adequate and strong immune response generated against this parasite.

Innate immunity modulation in the duodenal mucosa induced by REM sleep deprivation during infection with Trichinella spirallis

“…Interestingly, the results obtained demonstrated that sleep deprivation and stress doesn’t produces differences in corticosterone levels at three conditions, sleep, stress and sleep deprivation. However, an increase was observed in the group of animals that were only infected33. We shown that even though sleep deprivation can be categorized as a type of stress, the main component of this is sleep loss, and the two stimuli have a differential effect in two compartments of the immune system, namely spleen and mesenteric lymph nodes; also, the populations responded different.…”

“…We find tha natural killer cells (NK+) are most responsive to sleep deprivation, and the stress response is more heterogeneous. However, in that study we did not evaluate other mechanisms of host defence33.…”

“…Studies on the experimental manipulation of sleep have focused on the effects of sleep deprivation over the neural functions and blood flow of the brain3132; however, the dynamic changes of the intestinal barrier due to sleep deprivation have not gained much attention. In a previous study by our group, we evaluated whether sleep deprivation causes the dysregulation of immune variables during an immune response against the helminth parasite T. spiralis 33. Since sleep deprivation is a form of stress per se, in that study we compared stress alone (consisting in movement restriction and single housing) with sleep deprivation in both control and infected rats.…”

“…The analysis of the cellular subpopulations was performed at 48 h of infection, because the analysis corresponds to the stage of establishment of the infection, and therefore the mechanisms to expel the parasite have not been established, in our previous study we observed that the parasite load did not show differentiation between the groups33. As for the analysis realized in the intestinal mucous membrane, we demonstrated that the conditions of deprivation of sleep (SD) and stress have a distinguishing modulating effect, which depends on the cellular type and on its location.…”

“…The infection procedure was performed as previously described33. Briefly, consisted in inserting a gastric catheter, injecting 1500 muscle larvae of T. spiralis suspended in 500 μl of 1x PBS directly into the upper stomach.…”