Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1

Villar, Silvina Raquel; Ronco, Marı́a Teresa; Bussy, Rodrigo Fernández; Roggero, Eduardo; Lepletier, Ailin; Manarin, Romina; Savino, Wilson; Pérez, Ana Rosa

doi:10.1371/journal.pone.0063814

Cited by 28 publications

(32 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although TNF‐α could contribute to mediate the adrenal response during T. cruzi infection, it persists in TNFR1 and TNFR2 KO mice most likely, because there is a more marked increase in IL‐1 production in these mice, a cytokine known to induce a strong stimulation of the HPA axis . Furthermore, TNF‐α appears to have an inhibitory effect on steroid synthesis by parasite‐infected adrenal cells …”

Section: Overview: Relevance Of Neuroendocrine Host Responses For Thementioning

confidence: 99%

Glucocorticoids and sympathetic neurotransmitters modulate the acute immune response to Trypanosoma cruzi

Roggero

Rey

Wildmann

et al. 2018

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

Evidence suggests that natural and adaptive immune responses can trigger neuroendocrine responses. Here, we discuss changes in the activity of the hypothalamus-pituitary-adrenal axis and in autonomic nerves, predominantly of the sympathetic nervous system, in a mouse model of acute infection with Trypanosoma cruzi. The endocrine response includes a marked increased release of glucocorticoid and a decrease of immune-stimulatory hormones, such as dehydroepiandrosterone sulfate, prolactin, and growth hormone during infection. These endocrine changes result in reduced proinflammatory cytokine production, increased regulatory/effector T cell ratio, and thymus atrophy. The sympathetic activity in the spleen of infected mice is also markedly reduced. However, the residual sympathetic activity can modulate the immune response to the parasite, as shown by increased mortality and production of proinflammatory cytokines in sympathetically denervated, infected mice. The outcome of the neuroendocrine response is the moderation of the intensity of the immune response to the parasite, an effect that results in delayed mortality in susceptible mice, and favors the course toward chronicity in more resistant animals.

show abstract

Section: Overview: Relevance Of Neuroendocrine Host Responses For Thementioning

confidence: 99%

Glucocorticoids and sympathetic neurotransmitters modulate the acute immune response to Trypanosoma cruzi

Roggero

Rey

Wildmann

et al. 2018

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…Together with the marked elevation in circulating gonadotropins (Tables 2 and 3; Hruska et al 2010;Jeffries et al 2011), which are known to upregulate tumor necrosis factor (Clark and Atwood 2011) and subsequently glucocorticoid synthesis (Villar et al 2013), there is a large growth of the adrenal glands that produce very high concentrations of glucocorticoids which has been postulated to drive tissue degeneration/dysfunction and death of salmon (Carruth et al 2000;Finch 1990;Hruska et al 2010). A similar adrenocortical mechanism impacting immune function has been proposed for the post-mating deaths of males from dasyurid marsupials (Antechinus stuartii and A. favipes) of eastern Australia (Bradley et al 1980;McDonald et al 1981), although in the larger dasyurid Dasyurus hallucatus, there is no evidence of elevated corticosteroid levels during male die-off (Oakwood et al 2001).…”

Section: Ratio Of Sex Steroid/gonadotropin As a Measure Of Dyotic Sigmentioning

confidence: 99%

Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species

et al. 2017

View full text Add to dashboard Cite

Post-reproductive lifespan varies greatly among species; human post-reproductive lifespan comprises~30-50% of their total longevity, while semelparous salmon and dasyurid marsupials post-reproductive lifespan comprises <4% of their total longevity. To examine if the magnitude of hypothalamic-pituitarygonadal (HPG) axis dyscrasia at the time of reproductive senescence determines post-reproductive lifespan, we examined the difference between pre-and postreproductive (1) circulating sex hormones and (2) the ratio of sex steroids to gonadotropins (e.g., 17β-estradiol/follicle-stimulating hormone (FSH)), an index of the dysregulation of the HPG axis and the level of dyotic (death) signaling post-reproduction. Animals with a shorter post-reproductive lifespan (<4% total longevity) had a more marked decline in circulating sex steroids and corresponding elevation in gonadotropins compared to animals with a longer post-reproductive lifespan (30-60% total longevity). In semelparous female salmon of short post-reproductive lifespan (1%), these divergent changes in circulating hormone concentration postreproduction equated to a 711-fold decrease in the ratio of 17β-estradiol/FSH between the reproductive and post-reproductive periods. In contrast, the decrease in the ratio of 17β-estradiol/FSH in iteroparous female mammals with long post-reproductive lifespan was significantly less (1.7-34-fold) post-reproduction. Likewise, in male semelparous salmon, the decrease in the ratio of testosterone/FSH (82-fold) was considerably larger than for iteroparous species (1.3-11-fold). These results suggest that (1) organisms with greater reproductive endocrine dyscrasia more rapidly undergo senescence and die, and (2) the contribution postreproduction by non-gonadal (and perhaps gonadal) tissues to circulating sex hormones dictates postreproductive tissue health and longevity. In this way, reproduction and longevity are coupled, with the degree of non-gonadal tissue hormone production dictating the rate of somatic tissue demise post-reproduction and the differences in post-reproductive lifespans between species.

show abstract

“…Further studies developed in Tc-infected mice suggested that an ACTH-GC dissociation phenomenon may also occur in this protozoan infection. In fact, findings recorded from a single time point along the course of the acute infection showed that higher circulating levels of GC coexisted with slight ACTH amounts (32,33), raising the view of a GC-driven negative feedback as playing a role in this regard.…”

Section: Introductionmentioning

confidence: 99%

Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

It is well-established that infectious stress activates the hypothalamus-pituitary-adrenal axis leading to the production of pituitary adrenocorticotropin (ACTH) and adrenal glucocorticoids (GCs). Usually, GC synthesis is mediated by protein kinase A (PKA) signaling pathway triggered by ACTH. We previously demonstrated that acute murine Chagas disease courses with a marked increase of GC, with some data suggesting that GC synthesis may be ACTH-dissociated in the late phase of this parasitic infection. Alternative pathways of GC synthesis have been reported in sepsis or mental diseases, in which interleukin (IL)-1β, prostaglandin E2 (PGE2), and/or cAMP-activated guanine nucleotide exchange factor 2 (EPAC2) are likely to play a role in this regard. Accordingly, we have searched for the existence of an ACTH-independent pathway in an experimental model of a major parasitic disease like Chagas disease, in addition to characterizing potential alternative pathways of GC synthesis. To this end, C57BL/6 male mice were infected with T. cruzi (Tc), and evaluated throughout the acute phase for several parameters, including the kinetic of GC and ACTH release, the adrenal level of MC2R (ACTH receptor) expression, the p-PKA/PKA ratio as ACTH-dependent mechanism of signal transduction, as well as adrenal expression of IL-1β and its receptor, EPAC2 and PGE2 synthase. Our results reveal the existence of two phases involved in GC synthesis during Tc infection in mice, an initial one dealing with the well-known ACTH-dependent pathway, followed by a further ACTH-hyporesponsive phase. Furthermore, inflamed adrenal microenvironment may tune the production of intracellular mediators that also operate upon GC synthesis, like PGE2 synthase and EPAC2, as emerging driving forces for GC production in the advanced course of Tc infection. In essence, GC production seems to be associated with a biphasic action of PGE2, suggesting that the effect of PGE2/cAMP in the ACTH-independent second phase may be mediated by EPAC2.

show abstract

Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1

Cited by 28 publications

References 34 publications

Glucocorticoids and sympathetic neurotransmitters modulate the acute immune response to Trypanosoma cruzi

Glucocorticoids and sympathetic neurotransmitters modulate the acute immune response to Trypanosoma cruzi

Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species

Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease

Contact Info

Product

Resources

About