Hypothalamus-pituitary-adrenal axis during Trypanosoma cruzi acute infection in mice.
Functional interactions between neuroendocrine and immune systems are mediated by similar ligands and receptors, which establish a bi-directional communication that is relevant for homeostasis. We investigated herein the hypothalamus-pituitary-adrenal (HPA) axis in mice acutely infected by Trypanosoma cruzi, the causative agent of Chagas' disease. Parasites were seen in the adrenal gland, whereas T. cruzi specific PCR gene amplification product was found in both adrenal and pituitary glands of infected mice. Histological and immunohistochemical analyses of pituitary and adrenal glands of infected animals revealed several alterations including vascular stasis, upregulation of the extracellular matrix proteins fibronectin and laminin, as well as T cell and macrophage infiltration. Functionally, we detected a decrease in CRH and an increase in corticosterone contents, in hypothalamus and serum respectively. In contrast, we did not find significant changes in the amounts of ACTH in sera of infected animals, whereas the serum levels of the glucocorticoid-stimulating cytokine, IL-6 (interleukin-6), were increased as compared to controls. When we analyzed the effects of T. cruzi in ACTH-producing AtT-20 cell line, infected cultures presented lower levels of ACTH and pro-opiomelanocortin production when compared to controls. In these cells we observed a strong phosphorylation of STAT-3, together with an increased synthesis of IL-6, suppressor of cytokine signaling 3 (SOCS-3) and inhibitor of activated STAT-3 (PIAS-3), which could explain the partial blockage of ACTH production. In conclusion, our data reveal that the HPA axis is altered during acute T. cruzi infection, suggesting direct and indirect influences of the parasite in the endocrine homeostasis.
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Ave. Brasil 4365, Manguinhos- 21045-900, Rio de Janeiro, Brazil.
Eliane
E
Corrêa-de-Santana
Marcelo
M
Paez-Pereda
Marily
M
Theodoropoulou
Oscar
O
Kenji Nihei
Yvonne
Y
Gruebler
Marcelo
M
Bozza
Eduardo
E
Arzt
Déa Maria Serra
DM
Villa-Verde
Ulrich
U
Renner
Johanna
J
Stalla
Günter Karl
GK
Stalla
Wilson
W
Savino
D000311:Adrenal Glands / Q000382:microbiology / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000378:metabolism; D000818:Animals; D014355:Chagas Disease / Q000503:physiopathology*; D003345:Corticosterone / Q000032:analysis / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000382:microbiology* / Q000502:physiology; D007031:Hypothalamus / Q000382:microbiology / Q000502:physiology; D015151:Immunoblotting; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010902:Pituitary Gland / Q000382:microbiology / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000382:microbiology*; D050828:Protein Inhibitors of Activated STAT / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis / Q000378:metabolism; D014349:Trypanosoma cruzi
D015850:Interleukin-6; D050828:Protein Inhibitors of Activated STAT; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone