Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro

• Grant number: 12/10653-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: January 01, 2013
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Marco Aurélio Ramirez Vinolo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Niels Olsen Saraiva Câmara ; Ricardo Ambrósio Fock ; Rui Curi
• Associated research grant(s): 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation, AP.JP2
• Associated scholarship(s): 17/06577-9 - Mechanisms involved in the protective effect of short-chain fatty acids against Clostridium difficile-associated colitis, BP.DR; 16/23142-3 - Interaction between HIF-1 and short-chain fatty acids in the intestine: what is the role of HIF-1 acetylation? , BP.DR; 14/22909-3 - Role of the short chain fatty acids and their receptor (GPR43) in the neutrophil death induced by anaerobic bacteria, BP.MS; 14/02560-6 - Role of Short chain fatty acids and their receptor (GPR43) in the immune response against Aggregatibacter actinomycetemcomitans in a mono-infection model, BP.MS

Abstract

The anaerobic bacteria Porphyromonas ginigivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) are involved with the development of infectious diseases including periodontitis and abscess. The destruction of these bacteria depends on the activation, migration and effector function of innate and adaptive cells. In this context, neutrophils are key cells. Once in the infected tissue, neutrophils act through different mechanisms with the aim of eliminating the bacteria including the production of reactive oxygen and nitrogen species, release of proteases and enzymes that chelate nutrients, which are essential to the survive of bacteria, phagocytosing and inducing the recruitment and activation of other leukocytes. By the other side, bacteria present mechanisms for evading the immune system including proteases, polyssacharide capsule, hemmaglutinin and lipopolyssacharides. For Pg and Aa, products of their metabolism such as the short chain fatty acids (acetate, propionate and butyrate), which modulate leukocyte function, can also affect the host response to them. This project aims to investigate the role of SCFAs and their receptor (GPR43) in the immune response to anaerobic bacteria in vitro and in vivo and the intracellular pathways involved. For this, neutrophils and macrophages isolated from bone marrow of mice will be incubated with bacteria and the SCFAs. We will also analyze the immune response in vivo in a model of periodontal disease and using a subcutaneous chamber. We hypothesize that these fatty acids produced in the context of infection by anaerobic bacteria affect the action of immune cells and the outcome of the infectious process. (AU)

Scientific publications

(16)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, CAROLINE MARCANTONIO; VIEIRA, ANGELICA THOMAZ; RAMIREZ VINOLO, MARCO AURELIO; OLIVEIRA, FERNANDO A.; CURI, RUI; MARTINS, FLAVIANO DOS SANTOS. The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases. CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2014. (12/50336-2, 12/10653-9, 12/50410-8)

MOREIRA, VANESSA; LOMONTE, BRUNO; RAMIREZ VINOLO, MARCO AURELIO; CURI, RUI; MARIA GUTIERREZ, JOSE; TEIXEIRA, CATARINA. An Asp49 Phospholipase A(2) from Snake Venom Induces Cyclooxygenase-2 Expression and Prostaglandin E-2 Production via Activation of NF-kappa B, p38MAPK, and PKC in Macrophages. Mediators of Inflammation, 2014. (12/10653-9, 07/03337-5)

ANTUNES, KRIST HELEN; FACHI, JOSE LUIS; DE PAULA, ROSEMEIRE; DA SILVA, EMANUELLE FRAGA; PRAL, LAIS PASSARIELLO; DOS SANTOS, ADARA AUREA; MALAQUIAS DIAS, GREICY BRISA; VARGAS, JOSE EDUARDO; PUGA, RENATO; MAYER, FABIANA QUOOS; et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. NATURE COMMUNICATIONS, v. 10, JUL 22 2019. (13/06810-4, 17/06577-9, 12/10653-9)

RODRIGUES, HOSANA G.; VINOLO, MARCO A. R.; SATO, FABIO T.; MAGDALON, JULIANA; KUHL, CAROLINA M. C.; YAMAGATA, ANA S.; PESSOA, ANA FLAVIA M.; MALHEIROS, GABRIELLA; DOS SANTOS, MARINILCE F.; LIMA, CAMILA; et al. Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats. PLoS One, v. 11, n. 10, OCT 20 2016. (13/06810-4, 12/10653-9)

MOREIRA, VANESSA; GUTIERREZ, JOSE MARIA; LOMONTE, BRUNO; RAMIREZ VINOLO, MARCO AURELIO; CURI, RUI; LAMBEAU, GERARD; TEIXEIRA, CATARINA. 12-HETE is a regulator of PGE(2) production via COX-2 expression induced by a snake venom group IIA phospholipase A(2) in isolated peritoneal macrophages. Chemico-Biological Interactions, v. 317, FEB 1 2020. (12/10653-9, 07/03337-5)

SATO, FABIO TAKEO; YAP, YU ANNE; CRISMA, AMANDA RABELLO; PORTOVEDO, MARIANA; MURATA, GILSON MASAHIRO; HIRABARA, SANDRO MASSAO; RIBEIRO, WILLIAN RODRIGUES; FERREIRA, CAROLINE MARCANTONIO; CRUZ, MAYSA MARIANA; BERTAGLIA PEREIRA, JOICE NAIARA; et al. Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism. CELLS, v. 9, n. 9, SEP 2020. (12/15774-9, 12/10653-9, 18/15313-8)

FACHI, JOSE LUIS; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; DA SILVA, BRUNA KARADI; CORREA, RENAN OLIVEIRA; PEREIRA DE ANDRADE, MIRELLA CRISTINY; DA FONSECA, DENISE MORAIS; BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; DE SALES E SOUZA, ERICKA LORENNA; et al. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. CELL REPORTS, v. 27, n. 3, p. 750+, APR 16 2019. (17/01451-7, 12/10653-9, 16/23142-3, 13/06810-4, 14/03002-7, 15/01507-7, 18/01753-6, 15/06134-4, 17/25679-7, 17/06577-9, 18/02208-1, 17/26366-2, 17/16280-3)

VIEIRA, ANGELICA T.; GALVAO, IZABELA; MACIA, LAURENCE M.; SERNAGLIA, ERICA M.; VINOLO, MARCO AURELIO R.; GARCIA, CRISTIANA C.; TAVARES, LUCIANA P.; AMARAL, FLAVIO A.; SOUSA, LIRLANDIA P.; MARTINS, FLAVIANO S.; et al. Dietary fiber and the short-chain fatty acid acetate promote resolution of neutrophilic inflammation in a model of gout in mice. Journal of Leukocyte Biology, v. 101, n. 1, p. 275+, JAN 2017. (12/10653-9, 14/22909-3)

RODRIGUES, HOSANA G.; SATO, FABIO TAKEO; CURI, RUI; VINOLO, MARCO A. R.. Fatty acids as modulators of neutrophil recruitment, function and survival. European Journal of Pharmacology, v. 785, p. 50-58, AUG 15 2016. (12/15774-9, 13/06810-4, 12/10653-9)

CORREA, RENAN OLIVEIRA; FACHI, JOSE LUIS; VIEIRA, ALINE; SATO, FABIO TAKEO; VINOLO, MARCO AURELIO R.. Regulation of immune cell function by short-chain fatty acids. CLINICAL & TRANSLATIONAL IMMUNOLOGY, v. 5, APR 2016. (12/15774-9, 14/02560-6, 12/10653-9)

FELLOWS, RACHEL; DENIZOT, JEREMY; STELLATO, CLAUDIA; CUOMO, ALESSANDRO; JAIN, PAYAL; STOYANOVA, ELENA; BALAZSI, SZABINA; HAJNADY, ZOLTAN; LIEBERT, ANKE; KAZAKEVYCH, JURI; et al. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. NATURE COMMUNICATIONS, v. 9, JAN 9 2018. (15/14105-4, 12/10653-9, 15/50379-1)

FACHI, JOSE LUIS; SECCA, CRISTIANE; RODRIGUES, PATRICIA BRITO; PINHEIRO DE MATO, FELIPE CEZAR; DI LUCCIA, BLANDA; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; RUNGUE, MARCELLA; ROCHA, VICTOR DE MELO; SATO, FABIO TAKEO; et al. Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2. JOURNAL OF EXPERIMENTAL MEDICINE, v. 217, n. 3, MAR 2020. (17/06577-9, 19/14342-7, 12/10653-9, 18/02208-1, 17/16280-3)

CORREA, R. O.; VIEIRA, A.; SERNAGLIA, E. M.; LANCELLOTTI, M.; VIEIRA, A. T.; AVILA-CAMPOS, M. J.; RODRIGUES, H. G.; VINOLO, M. A. R.. Bacterial short-chain fatty acid metabolites modulate the inflammatory response against infectious bacteria. Cellular Microbiology, v. 19, n. 7, JUL 2017. (12/10653-9)

GALVAO, IZABELA; TAVARES, LUCIANA P.; CORREA, RENAN O.; FACHI, JOSE LUIS; ROCHA, VITOR MELO; RUNGUE, MARCELA; GARCIA, CRISTIANA C.; CASSALI, GEOVANNI; FERREIRA, CAROLINE M.; MARTINS, FLAVIANO S.; et al. The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung. FRONTIERS IN IMMUNOLOGY, v. 9, FEB 20 2018. (12/10653-9, 14/22909-3)

FERREIRA, CAROLINE MARCANTONIO; VIEIRA, ANGELICA THOMAZ; RAMIREZ VINOLO, MARCO AURELIO; OLIVEIRA, FERNANDO A.; CURI, RUI; MARTINS, FLAVIANO DOS SANTOS. The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2014, p. 12-pg., 2014-01-01. (12/50410-8, 12/10653-9, 12/50336-2)

MOREIRA, VANESSA; LOMONTE, BRUNO; RAMIREZ VINOLO, MARCO AURELIO; CURI, RUI; MARIA GUTIERREZ, JOSE; TEIXEIRA, CATARINA. An Asp49 Phospholipase A(2) from Snake Venom Induces Cyclooxygenase-2 Expression and Prostaglandin E-2 Production via Activation of NF-kappa B, p38MAPK, and PKC in Macrophages. Mediators of Inflammation, v. 2014, p. 10-pg., 2014-01-01. (07/03337-5, 12/10653-9)