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Effect of ArtinM administration, associated with antifungals drugs, on the course of Cryptococcus neoformans infection

Grant number: 19/13979-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): October 31, 2020
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Thiago Aparecido da Silva
Grantee:Edanielle Silva de Moura
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Fungal infections, due commit millions of lives each year, mainly immunocompromised individuals, nevertheless are neglected for public health policies. Most antifungal drugs of agents toxic to fungi can cause side effects in the patient. In this context, studies have been evaluating the establishment of immunotherapies favoring an effector antifungal response, which is essential the balance between T helper (Th) cells 1 and 2. In this scenario, the use of immunomodulatory agents, associated or not with antifungal therapies currently available for the treatment of systemic fungal infections, shows great interest. We will investigate whether the immunomodulatory activity of ArtinM, associated with the induction of Th1 immune response, could favor the resolution of Cryptococcus gattii infection. For this, will be considered the use of protocols for the therapeutic administration of ArtinM, intranasal or intratracheal route, the association of ArtinM administration with antifungal drugs, after the infection by C. neoformans. The use of ArtinM is related to its immunomodulatory activity reported in the resolution of infections by various intracellular pathogens, as in the experimental paracoccidioidomycosis. Our proposal intends to explore the association or not of immunotherapy agents, as ArtinM, with antifungal drugs to treat a disease caused by a fungus of global distribution. We reinforced the initial proposal through preliminary results, which the ArtinM administration promoted a significant decrease of fungal burden in the lungs of mice infected with C. gattii. Our aim will be analyzed with the following procedures: determination of the survival curve, serum and pulmonary levels of cytokines, fungal burden in the lungs and brain, quantification of reactive species of oxygen and nitrogen in the lung, cellular phenotypic in lung, levels of expression of factors inductors of cell differentiation, levels of GXM and histopathological evaluation of the lung and brain, in the C. neoformans infection model.

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