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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity

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Author(s):
Komegae, Evilin N. [1] ; Fonseca, Monique T. [1] ; Cruz-Machado, Sanseray da Silveira [2] ; Turato, Walter M. [3] ; Filgueiras, Luciano R. [1] ; Markus, Regina P. [2] ; Steiner, Alexandre A. [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmunol Sepsis Lab, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biosci, Lab Chronopharmacol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 10, JUN 28 2019.
Web of Science Citations: 0
Abstract

The mechanisms by which obesity may alter immune responses to pathogens are poorly understood. The present study assessed whether the intrinsic responsiveness of resident macrophages to bacterial lipopolysaccharide (LPS) is reprogrammed in high-fat diet (HFD)-induced obesity. Macrophages from adipose tissue, lung alveoli, and the peritoneal cavity were extracted fromobese rats on a HFD or fromtheir lean counterparts, and subsequently studied in culture under identical conditions. CD45(+)/CD68(+) cells (macrophages) were abundant in all cultures, and became the main producers of TNF-alpha upon LPS stimulation. But although all macrophage subpopulations responded to LPS with an M1-like profile of cytokine secretion, the TNF-alpha/IL-10 ratio was the lowest in adipose tissue macrophages, the highest in alveolar macrophages, and intermediary in peritoneal macrophages. What is more, diet exerted qualitatively distinct effects on the cytokine responses to LPS, with obesity switching adipose tissue macrophages to a more pro-inflammatory program and peritoneal macrophages to a less pro-inflammatory program, while not affecting alveolar macrophages. Such reprogramming was not associated with changes in the inflammasome-dependent secretion of IL-1 beta. The study further shows that the effects of diet on TNF-alpha/IL-10 ratios were linked to distinct patterns of NF-kappa B accumulation in the nucleus: while RelA was the NF-kappa B subunit most impacted by obesity in adipose tissue macrophages, cRel was the subunit affected in peritoneal macrophages. It is concluded that obesity causes dissimilar, site-specific changes in the responsiveness of resident macrophages to bacterial LPS. Such plasticity opens new avenues of investigation into the mechanisms linking obesity to pathogen-induced immune responses. (AU)

FAPESP's process: 12/03831-8 - Linking energy balance to systemic inflammation: role of leptin
Grantee:Alexandre Alarcon Steiner
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 18/03418-0 - Hypothermia in Sepsis: causes and consequences
Grantee:Alexandre Alarcon Steiner
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 14/03719-9 - Role of leptin in regulation of systemic inflammation
Grantee:Evilin Naname Komegae
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
Grantee:Regina Pekelmann Markus
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/04557-5 - The activation of immune-pineal axis by high-fat diet
Grantee:Sanseray da Silveira Cruz Machado
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 16/04921-1 - Arterial tonus in septic shock: a new facet to an old problem.
Grantee:Alexandre Alarcon Steiner
Support Opportunities: Regular Research Grants
FAPESP's process: 17/13350-0 - The temperature negatively regulates the microbicidal activity of macrophages: why do they kill more in hypothermia?
Grantee:Monique Thaís Costa Fonseca
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/17407-9 - Molecular programs involved in balance of SOCS-1/MyD88 expression in macrophages from individuals with diabetes and consequences in response to infection
Grantee:Luciano Filgueiras Ribeiro Junior
Support Opportunities: Scholarships in Brazil - Post-Doctoral