Expression of TLR-2, TLR-4 receptors in leukocytes from chronic kidney diseases (CKD) patients

• Grant number: 11/51496-0
• Support Opportunities: Regular Research Grants
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Aparecida Dalboni
• Grantee: Maria Aparecida Dalboni
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Bacterial infections are the first cause of hospitalization and second cause of mortality in chronic kidney diseases (CKD) patients, suggesting an immunodeficiency in this population to eliminate pathogens. It has been described an important association between a depressed immunologic response in CKD patients and presence of uremic toxins. The uremic toxins has been reported to reduce reactive oxygen species generation, phagocytosis, quimiotaxia, a high apoptosis rate of neutrophils (PMN) and low synthesis of cytokines by monocytes; resulting in adverse effect in some systems and decreased capability to response to infectious pathogens. However, any study was conducted to evaluate the effects of uremic toxins on pattern-recognition receptors (PRRs) expression in leukocytes that recognize pathogen-associated molecular patterns (PAMPs). PRRs are also responsible to initiate an immunological response against microbial pathogens. Recently, it has been reported that a receptors group called Toll-like receptors (TLRs) play an essential role on host defense through of recognition of PAMPs. However, few studies have been conducted to evaluate alterations of TLRs expression in neutrophils, monocytes and lymphocytes from CKD patients. The cause of cellular alteration and association with immunological dysfunction in CKD patients, remain unclear. Therefore, to investigate if uremic toxins cause lost function or change on TLRs expression in leukocytes could offer new knowledge on infection mechanisms in uremic patients and future therapeutics strategies. The aims of this study are: 1) to evaluate TLR-2 , TLR-4 and MyD88 expression in neutrophils, monocytes and lymphocytes from CKD pre-dialysis patients and hemodíalysis; 2) to evaluate the effect of uremic serum "in vitro" on TLR-2 , TLR-4 and MyD88 expression in neutrophils, monocytes and lymphocytes from healthy volunteers and 3) to evaluate the effect of uremic serum "in vitro" plus stimulated and unstimulated by lipopolysaccharide (LPS) and peptidoglycan (PG) on TLR-2 , TLR-4 and … (AU)

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)

GRABULOSA, CAREN C.; MANFREDI, SILVIA R.; CANZIANI, MARIA E.; QUINTO, BEATA M. R.; BARBOSA, RODRIGO B.; REBELLO, JACQUELINE F.; BATISTA, MARCELO C.; CENDOROGLO, MIGUEL; DALBONI, MARIA A.. Chronic kidney disease induces inflammation by increasing Toll-like receptor-4, cytokine and cathelicidin expression in neutrophils and monocytes. Experimental Cell Research, v. 365, n. 2, p. 157-162, APR 15 2018. (11/51496-0)