PARTICIPATION OF NOD-LIKE RECEPTORS ON INFLAMMATORY RESPONSE IN POLYMICROBIAL SEPSIS

• Grant number: 08/11593-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2009
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Fabiane Sônego
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 07/51247-5 - Mediators involved in the genesis of pain and the migration of leukocytes and in sepsis, AP.TEM

Abstract

Sepsis is a systemic inflammatory response due to an infection. The development of the local inflammatory response and, consequently, neutrophil recruitment is a critical process to control of an infection. Our group has showed the association between neutrophil migration to infectious site and the survival of animals in experimental severe sepsis model. Recently, we demonstrated that Toll-like receptor (TLR)2- or TLR4-defective mice present increased resistance to severe sepsis. We observed that the excessive activation of these receptors on circulation is able to reduce the neutrophil ability to be responsive to chemotatic stimulus, and, consequently, inhibits the migration of these cells to infectious site, leading to the death of the animal. Recently, a new family of receptors that recognize pathogens, called NOD-like receptors (NLRs), was described and related to the intracellular protection against pathogens. NOD1 and NOD2 recognize constituents of cell wall of Gram-negative and Gram-positive bacteria, respectively, and active pathways that are involved on inflammatory response. Considering the lack of studies about the role of NLRs in polymicrobial sepsis, the aim of this project is evaluate the participation of these receptors on local and systemic inflammatory response during polymicrobial sepsis.

Scientific publications

(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)

SONEGO, FABIANE; CASTANHEIRA, FERNANDA VARGAS E SILVA; FERREIRA, RAPHAEL GOMES; KANASHIRO, ALEXANDRE; VITORINO GONCALVES LEITE, CAIO ABNER; NASCIMENTO, DANIELE CARVALHO; COLON, DAVID FERNANDO; BORGES, VANESSA DE FATIMA; ALVES-FILHO, JOSE CARLOS; CUNHA, FERNANDO QUEIROZ. Paradoxical Roles of the neutrophil in Sepsis: Protective and Deleterious. FRONTIERS IN IMMUNOLOGY, v. 7, APR 26 2016. (08/11593-4, 11/19670-0)

SONEGO, FABIANE; CASTANHEIRA, FERNANDA V. S.; HORTA, CATARINA V.; KANASHIRO, ALEXANDRE; CZAIKOSKI, PAULA G.; ZAMBONI, DARIO S.; ALVES-FILHO, JOSE CARLOS; CUNHA, FERNANDO Q.. The host control of a clinical isolate strain of P-aeruginosa infection is independent of Nod-1 but depends on MyD88. Inflammation Research, v. 67, n. 5, p. 435-443, MAY 2018. (08/11593-4, 11/19670-0)

SONEGO, FABIANE; CASTANHEIRA, FERNANDA V. S.; CZAIKOSKI, PAULA G.; KANASHIRO, ALEXANDRE; SOUTO, FABRICIO O.; FRANCA, RAFAEL O.; NASCIMENTO, DANIELE C.; FREITAS, ANDRESSA; SPILLER, FERNANDO; CUNHA, LARISSA D.; et al. MyD88-, but Not Nod1- and/or Nod2-Deficient Mice, Show Increased Susceptibility to Polymicrobial Sepsis due to Impaired Local Inflammatory Response. PLoS One, v. 9, n. 8, AUG 1 2014. (08/11593-4, 11/19670-0)