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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1330094

Microbiota modulates the steroid response to acute immune stress in male mice

Karla Vagnerová1* Taťána Gazárková2 Martin Vodička1 Peter Ergang1 Petra Klusoňová1 Tomáš Hudcovic3 Dagmar Srutkova3 Petra Hermanova3 Lucie Nováková2 Jiří Pácha1, 4
  • 1Laboratory of Epithelial Physiology, Institute of Physiology, Academy of Sciences of the Czech Republic (ASCR), Czechia
  • 2Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Czechia
  • 3Laboratory of Gnotobiology, Institute of Microbiology (ASCR), Czechia
  • 4Department of Physiology, Division of Biology, Faculty of Science, Charles University, Czechia

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Microbiota play a role in shaping the HPA-axis response to psychological stressors. To examine the role of microbiota in response to acute immune stressor, we stimulated the adaptive immune system by anti-CD3 antibody injection and investigated the expression of adrenal steroidogenic enzymes and profiling of plasma corticosteroids and their metabolites in specific pathogen-free (SPF) and germ-free (GF) mice. Using UHPLC-MS/MS, we showed that 4 hours after immune challenge the plasma levels of pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone (CORT), 11-dehydroCORT and their 3-, 5-, and 20-reduced metabolites were increased in SPF mice, but in their GF counterparts, only CORT was increased. Neither immune stress nor microbiota changed the mRNA and protein levels of enzymes of adrenal steroidogenesis. In contrast, immune stress resulted in downregulated expression of steroidogenic genes (Star, Cyp11a1, Hsd3b1, Hsd3b6) and upregulated expression of genes of the 3-hydroxysteroid oxidoreductase pathway (Akr1c21, Dhrs9) in the testes of SPF mice. In the liver, immune stress downregulated the expression of genes encoding enzymes with 3-hydroxysteroid dehydrogenase (HSD) (Hsd3b2, Hsd3b3, Hsd3b4, Hsd3b5), 3-HSD (Akr1c14), 20-HSD (Akr1c6, Hsd17b1, Hsd17b2) and 5-reductase (Srd5a1) activities, except for Dhrs9, which was upregulated. In the colon, microbiota downregulated Cyp11a1 and modulated the response of Hsd11b1 and Hsd11b2 expression to immune stress. These data underline the role of microbiota in shaping the response to immune stressor. Microbiota modulates the stress-induced increase in C21 steroids, including those that are neuroactive that could play a role in alteration of HPA axis response to stress in GF animals.

Keywords: immune stress, Gut Microbiota, germ-free, Mice, anti-CD3, Steroids, Steroidogenic genes

Received: 30 Oct 2023; Accepted: 18 Jan 2024.

Copyright: © 2024 Vagnerová, Gazárková, Vodička, Ergang, Klusoňová, Hudcovic, Srutkova, Hermanova, Nováková and Pácha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Karla Vagnerová, Laboratory of Epithelial Physiology, Institute of Physiology, Academy of Sciences of the Czech Republic (ASCR), Prague, 142 20, Prague, Czechia