Macrophage Polarization in Chagas Disease

Submitted by Luciane Willcox ([email protected]) on 2016-08-30T15:29:19Z No. of bitstreams: 1 macrophage-polarization-in-chagas-disease-2155-9899-1000317.pdf: 660126 bytes, checksum: 4da541af34b392da2847a7ef5bd1082a (MD5)Approved for entry into archive by Luciane Willcox ([email protected]) on 2016-08-30T16:22:50Z (GMT) No. of bitstreams: 1 macrophage-polarization-in-chagas-disease-2155-9899-1000317.pdf: 660126 bytes, checksum: 4da541af34b392da2847a7ef5bd1082a (MD5)Made available in DSpace on 2016-08-30T16:22:50Z (GMT). No. of bitstreams: 1 macrophage-polarization-in-chagas-disease-2155-9899-1000317.pdf: 660126 bytes, checksum: 4da541af34b392da2847a7ef5bd1082a (MD5) Previous issue date: 2015-04-06Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunopatologia Experimental. Londrina, PR, Brasil.Macrophages are terminally differentiated cells of the mononuclear phagocytic system, which play an indispensable role in the maintenance of homeostasis and defense. Macrophages can be phenotypically polarized by the microenvironment to mount specific functional responses. Polarized macrophages can be broadly classified into two main groups: classically activated macrophages (M1), whose prototypical activating stimuli are IFN-γ and LPS, and alternatively activated macrophages (M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1β or LPS) and M2c (IL-10, TGF-β or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, while M2 macrophages support Th2- associated effector functions. Here we review the main functions of polarized macrophages in Chagas disease and discuss their potential value in evaluating disease severity

Aspirin Modulates Innate Inflammatory Response and Inhibits the Entry of Trypanosoma cruzi in Mouse Peritoneal Macrophages

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite’s life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host’s cyclooxygenase (COX) enzyme during T. cruzi invasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused marked inhibition of T. cruzi infection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1β and nitric oxide (NO∙) by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2 (PGE2) restored the invasive action of T. cruzi in macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2, NO∙, and lipoxins are involved in the regulation of anti-T. cruzi activity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response to T. cruzi infection as well as adding a new perspective to specific immune interventions