Leukotrienes as modulators of innate immunity to fungi.

Author(s)

Mariana Morato Marques

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2012-08-30

Examining board members

Sonia Jancar Negro; Vera Lucia Garcia Calich; Ana Campa; Antonio Condino Neto; Alexandra Ivo de Medeiros

• Advisor: Sonia Jancar Negro

Abstract

Leukotrienes (LTs) are lipid mediators derived from arachidonic acid. There is evidence that innate immunity receptors and leukotrienes receptors interact and amplify macrophage effector functions. We investigated if LTs receptors modulate phagocytosis and microbicidal activity mediated by Mannose receptor, Dectin-1 and PTX3 in alveolar macrophages (AMs) and the molecular mechanisms involved. Our results showed that: 1) AMs produce LTs when stimulated with C.albicans, Zy, Zy-PTX3; 2) LTs enhance phagocytosis of C.albicans and Zymosan, but not Zy-PTX3. This is dependent on: recognition via mannose receptor (LTB4) and Dectin-1 (LTD4); integrity of lipid rafts; its action on actin polimerization mechanisms; enhancement of F-actin levels by induction of Cofilin-1 inactivation; activation of LIMKs that regulate Cofilin-1; activation of PKC<font face=\"Symbol\">d and PI3K3) LTs enhance killing of C.albicans by activation of NADPH oxidase. Taken together, our results showed that LTs specifically influence signaling programs of keys PRRs. (AU)

• FAPESP's process: 08/03722-9 - Mollecular aspects of pentraxin 3 and leukotrienes in phagocytosis and microbicidal activity of alveolar macrophages
• Grantee: Mariana Morato Marques
• Support Opportunities: Scholarships in Brazil - Doctorate