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

Abstract

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.

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

“…Rats were weighed daily and killed after 3 days of treatment to obtain blood and tissues for different studies. We found a significant increment in the levels of ACTH and corticosterone in the IS group, in agreement with the sustained input of the hypothalamus-pituitary-adrenal axis [2,4] . We observed increments in liver and spleen weights in both infected (I and IS) groups, although the thymus size remained unchanged.…”

“…A similar fungal burden was detected in the kidneys and spleens of infected rats, whereas livers were heavily colonized in infected stressed hosts. Stained liver sections showed budding yeasts enclosed inside large and well-developed granulomas in I rats [2] , whereas invasive hyphae or pseudohyphae forms predominated in IS hosts exhibiting incomplete granulomatous lesions [2,5] . As TNF-␣ is crucial for developing a protective inflammatory reaction and antigens of the fungal cell wall induce TNF-␣ production [6] , we evaluated the production of this cytokine under the different experimental conditions.…”

“…3 ! 10 8 viable C. albicans cells and we started the stress exposure immediately after infection (IS group) [2] . The stress paradigm lasted 3 days and…”

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

Stress-Induced Downregulation of Macrophage Phagocytic Function Is Attenuated by Exercise Training in Rats

“…Restraint stress has been shown to suppress the uptake of zymosan as well as the clearance of carbon particles in vitro [7] . Rodriguez-Galan et al [8] showed that during infection with Candida albicans , the exposure to stress contributes to the spread of the fungus and downregulates critical functions of phagocytic macrophages.Regular moderate physical exercise (physical training) has been reported to lower the susceptibility to viral and bacterial infections [9] . Woods et al [10] verified that moderate treadmill running (30 min/day at 18 m/ min, 5% grade) conducted 3 days prior to and 14 days after tumor implantation resulted in a small increase in the number and phagocytic activity of intratumoral macrophages when compared with the sedentary group.…”