Chronic Varied Stress Modulates Experimental Autoimmune Encephalomyelitis in Wistar Rats

Objective: Candidiasis is a prototypic opportunistic fungal disease that may follow severe modulations of the immune system of the host. The purpose of this study was to evaluate which innate immune mechanisms involved in the protection against fungal invasion are impaired under stress conditions. Methods: Wistar rats were infected intraperitoneally with Candida albicans and immediately exposed to chronic varied stress (CVS) over 10 days (CVS; Ca-S); the fungal burden (CFU), histopathological lesion and ACTH levels were evaluated. Additionally, functional assessment of peritoneal cells (PC) included the phagocytic and anticandidacidal activities and the production of H₂O₂ and NO. Results: In the only infected animals (Ca), C. albicans colonization stimulated an efficient inflammatory response, while in Ca-S rats poor tissue reactions were associated with increased CFU in livers and kidneys (p < 0.05, Ca vs. Ca-S). Whereas the phagocytic process was not modified, the candidacidal activity of PC was significantly decreased after the application of CVS (p < 0.001, Ca vs. Ca-S). The H₂O₂ production by macrophages and neutrophils was downregulated by the infection, and while at early intervals these cells possessed a residual oxidative capacity, by day 10, the production of this metabolite was blocked. Spontaneous NO production by macrophages was significantly increased in both Ca and Ca-S animals (p < 0.001), but in stressed rats, this reactive nitrogen intermediate was noticeably downregulated (p < 0.05, Ca vs. Ca-S). The hyperactivity of hypothalamus-pituitary-adrenal axis after exposure to stress was confirmed by an increase in baseline plasma ACTH levels. Conclusion: These results show that during infection with C. albicans, the exposure to CVS contributes to the spread of the fungus and downregulates critical functions of phagocytic cells involved in the control of this opportunistic pathogen.

Section: Stress Proceduresmentioning

confidence: 99%

Impaired Activity of Phagocytic Cells in <i>Candida albicans</i> Infection after Exposure to Chronic Varied Stress

Rodríguez-Galán

Correa

Cejas

et al. 2001

“…Interestingly, Whitacre et al [12] reported that 10 days after termination of the stress period, clinical signs returned and were as severe or more severe than in control nonstressed animals. Correa et al [13] showed that the application of varied chronic stressors (swimming, water deprivation, restraint, crowding, sound for 14 days) before EAE induction with myelin basic protein suppressed EAE in Wistar rats. On the other hand, they demonstrated that disease was exacerbated if stress was administered after immunization.…”

Section: Chronic Stressorsmentioning

confidence: 99%

“…[12] Repeated chronic Stress prior to immunization suppresses EAE Stress effect depends on sex, strain and time of day Correa et al [13] Repeated chronic Stress prior to immunization suppresses EAE Stress after immunization and continued until later disease stage (day 14) exacerbates EAE Kuroda et al [14] Repeated chronic Stress during preclinical stage suppresses EAE Stress after clinical symptom onset exacerbates EAE Teunis et al [16] Acute stressor Early life stress (maternal deprivation) enhances susceptibility to EAE later Chandler et al [17] Acute stressor Acute stress shortly after immunization exacerbates disease and increases blood-brain barrier…”

Section: Stress Response Pathways and Disability Progressionmentioning

confidence: 99%

Stress and Disease Progression in Multiple Sclerosis and Its Animal Models

Gold¹,

Heesen

2006

Since the first description of multiple sclerosis (MS) by Charcot, stress has been hypothesized to be a potential trigger of relapses. In recent years, data from observational studies in MS patients have provided some support for an association between stress and MS relapses. Furthermore, studies employing the MS animal model experimental autoimmune encephalomyelitis have shown that certain stressors can exacerbate the disease if administered prior to disease induction. Several lines of research have explored the 2 major stress response systems – the hypothalamic-pituitary-adrenal axis and the autonomic nervous system – and their relation to disease course in MS and experimental autoimmune encephalomyelitis. These studies provide evidence that insensitivity of the immune system to signals from these systems may play a role in inflammatory events. These findings can be integrated into a biological model of stress response system alterations in MS.

“…included cold swimming, restraint and food deprivation [2,3] . Additionally, uninfected unstressed (N), stressed (S) or infected (I) groups were included as controls.…”

mentioning

confidence: 99%

Immune Neuroendocrine Interactions during a Fungal Infection in Immunocompetent or Immunosuppressed Hosts

Rodríguez-Galán¹,

Sotomayor²,

Cano³

et al. 2010

Self Cite

The yeast Candida albicans belongs to the microflora of healthy individuals, although it can infect a variety of tissues ensuing changes in the host’s immune status. To evaluate the effect of neuroendocrine input on the early immune response during the fungal infection, we use a 3-day paradigm of chronic varied stress in Wistar rats infected with C. albicans. We find that stress mediators contribute to the spread of the fungus and downregulate critical functions of phagocytic cells at the infection site. Phenotypic and functional alterations of effector cells account for the decreased resistance to candidiasis and condition the development of the adaptive response. Stressed hosts exhibit a higher fungal burden in kidneys and livers associated with hyphal forms. The hepatic inflammatory reaction is compromised with severe steatosis, increment of functional enzymes, marked lipid peroxidation and hepatocyte apoptosis. Moreover, infection-related sickness symptoms are significantly increased by exposure to stress with anorexia, weight loss, lack of leptin and depletion of glycogen depots. Food deprivation exacerbates the liver injury. Stress mediators perturb the complex immune and metabolic program that operates early during fungal spread and promotes severe tissue damage.