Determination of innate and adaptive mechanisms in the recognition of Sporothrix brasiliensis by macrophages and dendritic cells

• Grant number: 18/07073-7
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): June 01, 2018
• Effective date (End): October 12, 2021
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Sandro Rogerio de Almeida
• Grantee: Grasielle Pereira Jannuzzi
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/04729-3 - Bases of cellular immune response in chromoblastomycosis and sporotrichosis: implications for vaccine therapy, AP.TEM

Abstract

In recent decades, there has been an increase in the incidence of fungal infections. This was mainly due to invasive medical interventions, long hospital stays, and increased numbers of immunocompromised patients due to infectious diseases such as HIV or immunodeficiency-inducing treatments such as immunosuppressants and drugs used to treat Cancer. Sporotrichosis presents as a subcutaneous mycosis caused by the dimorphic fungus Sporothrix sp. which affects man and a wide variety of animals such as dogs, cats, cattle and horses. Soil rich in organic matter and in vegetation, bark of trees and warm and humid environments are the habitat of Sporothrix sp. in saprophytic form. Sporotrichosis is acquired through the traumatic implant of Sporothrix sp. in the dermis, caused by the handling of plants and soil, and also by the contamination of wounds. In recent decades the domestic feline has been gaining evidence in the transmission of sporotrichosis through scratching and biting. The development of lesions at the fungus inoculation site is related to the host's immune system, amount and virulence of the inoculated agent. Clinically, this infection can be classified as cutaneous (fixed, lymphocutaneous and disseminated) and extracutaneous (joint, bone, ocular, pulmonary and systemic). MARIMON et al. (2007) clearly defined that the species Sporothrix schenckii consisted of a complex involving 6 species (S. brasiliensis, S. albicans, S. luriei, S. globosa, S. mexicana and S. Schenckii). Since this publication, the literature records few studies involving these new species, and the understanding of the mechanisms of immune response to these microorganisms.In the city of Rio de Janeiro and metropolitan region, an important epidemic has been described since 1998, in which sporotrichosis has been affecting humans, cats and dogs. Interestingly, the species related to the epidemic in the state and feline sporotrichosis is S. brasiliensis.Although the immune defense mechanisms against Sporothrix sp. are not well established, it is known that the innate, cellular and humoral response plays an important role in the control of infection. Cells that are part of cellular immunity recognize the antigens of the fungus activating CD4 + T cells and macrophages, causing them to produce proinflammatory cytokines that are necessary for the development of granuloma formation, which is a critical and essential component in the defense of the host against pathogens. Therefore, the research involving the S. schenckii complex, specifically the S. brasiliensis species and its interaction with the host, is necessary to confirm, clarify and deepen the knowledge about the relationships of these new species with the disease, diagnosis and treatment. Numerous questions, previously unanswered, may now be elucidated in the light of new investigations. In this context, the present study is justified by the need to understand the mechanisms employed by the innate and acquired immunity in order to investigate the response profile of macrophages, dendritic cells and T lymphocytes to Sporothrix brasiliensis species. (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)

JANNUZZI, GRASIELLE PEREIRA; DE ALMEIDA, JOSE ROBERTO FOGACA; PAULO, LARISSA NEVES MONTEIRO; DE ALMEIDA, SANDRO ROGERIO; FERREIRA, KAREN SPADARI. Intracellular PRRs Activation in Targeting the Immune Response Against Fungal Infections. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, OCT 20 2020. (18/07073-7)