Importance of natural killer cells in sporotrichosis: correlation with immunological memory?

• Grant number: 22/06947-9
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Iracilda Zeppone Carlos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The ability to form immunological memory is considered a hallmark of adaptive immunity. However, increasing evidence suggests that innate immune cells, including natural killer cells, can also "remember" prior exposures to certain stimuli, responding at a higher magnitude upon a secondary immune stimulation. First described in 1975, based on their capability to eliminate allogeneic tumor cells without the need for previous sensitization and in the absence of recombined antigen receptors, NK cells contribute to effective innate immune responses and provide the first important line of defense against parasites, viruses, cancer, and, as showed more recently, fungi. Add to that our recent findings showing that NK cells play a pivotal role in the in vivo protection against Sporothrix schenckii, one of the causative agents of sporotrichosis. When responding to infection or immunization with diverse viruses, NK cells can develop into long-lived memory cells, capable of more robust cytotoxic responses and higher IFN-³ production. There is not, however, a single study regarding the induction of memory NK cells during infections by non-viral pathogens, such as bacteria and fungi. In this sense, recent findings showed that Cryptococcus and Candida can be specifically recognized and killed by NK cells, making it plausible that pathogen-specific memory NK cells can develop against fungi. Accordingly, we propose to assess, using a murine model of Sporothrix infection, whether a fungal infection is able to induce memory NK cells, as well as their importance to host protection in a subsequent challenge with this same pathogen. (AU)