Phenotypic and functional changes on phagocytic cells recruited at the site of Candida albicans infection after chronic varied stress exposure.

The transition of Candida albicans from commensalism to pathogenicity is associated with the immune status of the host; resistance to fungus involves macrophages (Mphi) and polymorphonuclear neutrophils (PMN), which act as effector cells. T-cell function is also involved. Previously, we found that in Wistar rats exposed to chronic varied stress (CVS) immediately after C. albicans infection (Ca-S group) some functions of phagocytic cells, such as killer activity and NO production, were strongly modified compared with unstressed, infected animals (Ca group). We examined the phenotypic and functional changes of these effector cells recruited at the site of C. albicans infection. The recruitment of peritoneal cells (PC) was markedly reduced in Ca-S animals and the arrival of Mphi and PMN was selectively diminished after CVS exposure. The integrin CD11b/CD18, implicated in migration and C. albicans phagocytosis, was downregulated in Mphi of Ca-S animals. The activation markers CD54 and MHC-II were upregulated in Mphi after fungal contact. The expression of CD54 was only changed in Ca-S rats. Finally, TNF-alpha production was reduced in PC of Ca-S animals, suggesting an impairment of functional activity. Taken together, the phenotypic and functional changes detected in effector cells may account for the decreased resistance to candidiasis seen in conjunction with CVS. The changes seen also expand our knowledge of the role of Mphi in the control of C. albicans dissemination.

Impaired activity of phagocytic cells in Candida albicans infection after exposure to chronic varied stress.

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 H(2)O(2) 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 H(2)O(2) 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.

[Basic aspects of neuroendocrinoimmunology]. / Aspectos básicos de la Neuroendocrinoinmunología (NEI).

The purpose of this article is to discuss basic aspects of the interplay between the neuroendocrine and the immune systems. Two pathways link the brain and the immune system: the autonomic nervous system and the neuroendocrine outflow via the pituitary. Most of the influence of the brain on immune events is exerted through the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, certain neurotransmitters, neuropeptides, and neurohormones affect immune function both in vivo and in vitro. Receptors for these molecules are present on immune cells. This cell-to-cell communication is bi-directional, since impulses from the immune system can affect many functions of the central nervous system. Cytokines released during the activation of the immune system, in turn, can alter the function of the HPA axis. In this context, we also describe our main findings working with a model of Candida albicans infection in rats exposed to chronic varied stress.

Aspectos básicos de la Neuroendocrinoinmunología (NEI). / [Basic aspects of neuroendocrinoimmunology]

The purpose of this article is to discuss basic aspects of the interplay between the neuroendocrine and the immune systems. Two pathways link the brain and the immune system: the autonomic nervous system and the neuroendocrine outflow via the pituitary. Most of the influence of the brain on immune events is exerted through the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, certain neurotransmitters, neuropeptides, and neurohormones affect immune function both in vivo and in vitro. Receptors for these molecules are present on immune cells. This cell-to-cell communication is bi-directional, since impulses from the immune system can affect many functions of the central nervous system. Cytokines released during the activation of the immune system, in turn, can alter the function of the HPA axis. In this context, we also describe our main findings working with a model of Candida albicans infection in rats exposed to chronic varied stress.

Chronic varied stress modulates experimental autoimmune encephalomyelitis in Wistar rats.

Stress disturbs homeostasis by altering the equilibrium of various hormones which have a significant impact on immune responses. Few studies have examined the influence of stressors on autoimmune disease in animal models. In our work, we studied the effects of long-term exposure (14 days) to chronic varied stress (CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar rats. We studied whether the exposure to CVS before or after the immune challenge would correlate with differences in the clinical course of the disease. We also examined whether the CVS would modulate the magnitude of the cellular or the humoral immune response. We observed opposite effects on the clinical signs in animals stressed before or after the immune challenge. The clinical signs of the disease were attenuated in animals stressed before but not after the immune challenge. Relationships were found in the modulation of the clinical severity related to the time of exposure to the CVS, the histological alterations and the proliferative results. Stressed animals with milder clinical signs presented an exacerbated humoral response against myelin antigens while stressed animals with more severe clinical symptoms exhibited a significantly diminished one. Besides, we detected the presence of specific IgG1 associated with the exposure to CVS before the induction of EAE. Our results show that, depending on the timing of the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a more pronounced humoral or cellular profile of the response.