Involvement of natural killer cells in infection induced by Sporothrix spp and its correlation with the vaccination

• Grant number: 23/18205-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• End date: September 30, 2027
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Adriana Fernandes de Deus
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Fungal infections affect millions of people around the world, causing everything from acute local infections to systemic diseases that can lead to death. Understanding the complex innate and adaptive immune mechanisms that protect humans from pathogenic fungi is therefore critical. Natural killer (NK) cells were first described in 1975, based on their ability to eliminate allogeneic tumor cells without the need for prior sensitization and in the absence of recombinant antigen receptors, and they contribute to effective innate immune responses and provide the important first line of defense against parasites, viruses, cancer and, as shown more recently, fungi. However, a growing body of evidence suggests that innate immune cells, including NK cells, can also "remember" previous exposures to certain stimuli, responding in greater magnitude to a secondary stimulus. Furthermore recent findings show that NK cells play a fundamental role in in vivo protection against Sporothrix schenckii. In response to infection or immunization with various viruses, NK cells can develop into long-lived memory cells capable of more robust cytotoxic responses and greater production of IFN-³. There is no information in the literature about the induction of memory NK cells in infections caused by non-viral pathogens, such as parasites and fungi. Therefore, we propose to investigate, using a murine model of Sporothrix spp infection, whether this fungal infection is capable of inducing memory NK cells, as well as their importance for protecting the host in a subsequent challenge with this same pathogen, enabling future use of these cells to obtain a better vaccine product.