Obesity-Induced Dysbiosis Exacerbates IFN-gamma Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection

Author(s):Show less -

Palma Albornoz, Sandra Patricia ^[1] ; de Campos Fraga-Silva, Thais Fernanda ^{[2, 1]} ; Gembre, Ana Flavia ^[2] ; de Oliveira, Romulo Silva ^[1] ; de Souza, Fernanda Mesquita ^[1] ; Rodrigues, Tamara Silva ^[1] ; Kettelhut, Isis do Carmo ^[2] ; Manca, Camila Sanches ^[3] ; Jordao, Alceu Afonso ^[4] ; Zambelli Ramalho, Leandra Naira ^[5] ; Martins Ribolla, Paulo Eduardo ^[6] ; Carlos, Daniela ^{[2, 1]} ; Deperon Bonato, Vania Luiza ^{[2, 1]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Basic & Appl Immunol Program, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Hlth Sci, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[6] Sao Paulo State Univ, Biotechnol Inst, BR-18607440 Botucatu, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 10, n. 7 JUL 2021.
• Web of Science Citations: 0

Abstract

The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-gamma levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4(+)IFN-gamma+IL-17(-) cells and IFN-gamma levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-gamma-mediated immunopathology. (AU)

• FAPESP's process: 17/21629-5 - Strategies to study pulmonary inflammation during comorbidities
• Grantee: Vânia Luiza Deperon Bonato
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/00774-1 - Interplay of the immune response in the obesity and tuberculosis
• Grantee: João Santana da Silva
• Support Opportunities: Regular Research Grants