Monocyte activation pathways of patients with paracoccidioidomycosis and dermatomycosis: Role of pattern recognition receptors (PRR) and implications for treatment

• Grant number: 15/25022-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2016
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Sandro Rogerio de Almeida
• Grantee: Sandro Rogerio de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The treatment of systemic mycoses is a challenge and the therapeutic failures and recurrences are common. Much of this framework is due to the little knowledge we have about the pathogenic mechanisms involved in the disease, which complicates the understanding of it, the development of new therapeutic strategies and detection of possible drug targets. Recently, several studies have demonstrated the involvement of receptors of the innate immune response in the control of infectious diseases.The pattern recognition receptors (PRR) as Nod (RLNs), tolls and C-type lectins, are elements of the innate immune response related to survey the intra and extracellular environment, recognizing molecular patterns associated with pathogens (PAMPs) or damage to the host (damps). Upon being activated, the receptors may form inflamassomos, platforms involved in caspase-1 activation and subsequently, the pro-inflammatory cytokines such as TNF-±, IL-1² and IL-18.The activity of PRRs / Inflamassomos been linked to various pathophysiological processes, such as diabetes, obesity and infectious disease (bacterial, viral and fungal). Particularly in the case of mycosis, the information is still incomplete, but indicate a key role of inflamassomos in control and defining a protective adaptive response (TH1 and TH17). Therefore, this project aims to clarify the immunological mechanisms involved in the interaction of PRRs with important pathogenic fungi, and thus more knowledge about the pathophysiology of paracoccidioidomycosis and ringworm, and a possible alternative in the treatment of these fungal infections. (AU)