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


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)

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Scientific publications (14)
(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)
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, . (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, . (15/14105-4, 12/10653-9, 15/50379-1)
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, . (12/10653-9)
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, . (17/06577-9, 19/14342-7, 12/10653-9, 18/02208-1, 17/16280-3)
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, . (12/10653-9, 14/22909-3)
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, . (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, . (13/06810-4, 17/06577-9, 12/10653-9)
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, . (12/15774-9, 12/10653-9, 18/15313-8)
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, . (07/03337-5, 12/10653-9)
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+, . (17/16280-3, 16/23142-3, 17/25679-7, 15/01507-7, 12/10653-9, 17/26366-2, 18/01753-6, 17/01451-7, 13/06810-4, 15/06134-4, 14/03002-7, 17/06577-9, 18/02208-1)
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, . (12/15774-9, 13/06810-4, 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, . (13/06810-4, 12/10653-9)
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+, . (12/10653-9, 14/22909-3)

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