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Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study

BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influen...

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Autores principales: Dos Santos, Déborah Cruz, de Souza Bittencout, Rafaela, Arêas, Iago Dórea, Pena, Larissa Silva C., Almeida, Carolline Florentino, de Brito Guimarães, Bruna Carolina, Dórea, Rafael Santos Dantas Miranda, Correia, Thiago Macêdo Lopes, Júnior, Manoel Neres Santos, Morbeck, Lorena Lôbo Brito, Dos Santos, Talita Costa, Souza, Clarissa Leal S., de Souza, Samira Itana, de Jesus Soares, Telma, Yatsuda, Regiane, Campos, Guilherme Barreto, Marques, Lucas Miranda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065996/
https://www.ncbi.nlm.nih.gov/pubmed/37004108
http://dx.doi.org/10.1186/s13293-023-00501-2
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author Dos Santos, Déborah Cruz
de Souza Bittencout, Rafaela
Arêas, Iago Dórea
Pena, Larissa Silva C.
Almeida, Carolline Florentino
de Brito Guimarães, Bruna Carolina
Dórea, Rafael Santos Dantas Miranda
Correia, Thiago Macêdo Lopes
Júnior, Manoel Neres Santos
Morbeck, Lorena Lôbo Brito
Dos Santos, Talita Costa
Souza, Clarissa Leal S.
de Souza, Samira Itana
de Jesus Soares, Telma
Yatsuda, Regiane
Campos, Guilherme Barreto
Marques, Lucas Miranda
author_facet Dos Santos, Déborah Cruz
de Souza Bittencout, Rafaela
Arêas, Iago Dórea
Pena, Larissa Silva C.
Almeida, Carolline Florentino
de Brito Guimarães, Bruna Carolina
Dórea, Rafael Santos Dantas Miranda
Correia, Thiago Macêdo Lopes
Júnior, Manoel Neres Santos
Morbeck, Lorena Lôbo Brito
Dos Santos, Talita Costa
Souza, Clarissa Leal S.
de Souza, Samira Itana
de Jesus Soares, Telma
Yatsuda, Regiane
Campos, Guilherme Barreto
Marques, Lucas Miranda
author_sort Dos Santos, Déborah Cruz
collection PubMed
description BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus. METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 μL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 μL of 10(–2) M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO(−2)); and hydrogen peroxide (H(2)O(2)) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO(−2), and H(2)O(2). The HPBMs were then removed for the analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05. RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO(−2), and H(2)O(2) when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO(−2), and H(2)O(2). The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs. CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.
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spelling pubmed-100659962023-04-03 Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study Dos Santos, Déborah Cruz de Souza Bittencout, Rafaela Arêas, Iago Dórea Pena, Larissa Silva C. Almeida, Carolline Florentino de Brito Guimarães, Bruna Carolina Dórea, Rafael Santos Dantas Miranda Correia, Thiago Macêdo Lopes Júnior, Manoel Neres Santos Morbeck, Lorena Lôbo Brito Dos Santos, Talita Costa Souza, Clarissa Leal S. de Souza, Samira Itana de Jesus Soares, Telma Yatsuda, Regiane Campos, Guilherme Barreto Marques, Lucas Miranda Biol Sex Differ Research BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus. METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 μL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 μL of 10(–2) M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO(−2)); and hydrogen peroxide (H(2)O(2)) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO(−2), and H(2)O(2). The HPBMs were then removed for the analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05. RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO(−2), and H(2)O(2) when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO(−2), and H(2)O(2). The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs. CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen. BioMed Central 2023-03-31 /pmc/articles/PMC10065996/ /pubmed/37004108 http://dx.doi.org/10.1186/s13293-023-00501-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Dos Santos, Déborah Cruz
de Souza Bittencout, Rafaela
Arêas, Iago Dórea
Pena, Larissa Silva C.
Almeida, Carolline Florentino
de Brito Guimarães, Bruna Carolina
Dórea, Rafael Santos Dantas Miranda
Correia, Thiago Macêdo Lopes
Júnior, Manoel Neres Santos
Morbeck, Lorena Lôbo Brito
Dos Santos, Talita Costa
Souza, Clarissa Leal S.
de Souza, Samira Itana
de Jesus Soares, Telma
Yatsuda, Regiane
Campos, Guilherme Barreto
Marques, Lucas Miranda
Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study
title Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study
title_full Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study
title_fullStr Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study
title_full_unstemmed Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study
title_short Effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to Staphylococcus aureus: an in vitro study
title_sort effects of 5α-dihydrotestosterone on the modulation of monocyte/macrophage response to staphylococcus aureus: an in vitro study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065996/
https://www.ncbi.nlm.nih.gov/pubmed/37004108
http://dx.doi.org/10.1186/s13293-023-00501-2
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