Study about the interaction between the invariant "Natural Killer" T limphocytes and B1 cells in immune response to Paracocciodioides brasiliensis

• Grant number: 13/01049-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2013
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Joes Nogueira Neto
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/50256-6 - B-1 cells: biology, relations with other cells of the immune system and participation in different experimental models, AP.TEM

Abstract

Paracocciodioidomicosis (PCM), caused by the fungus Paracoccidioides brasiliensis (Pb), it is one of the most prevalent systemic human mycosis in Latin America. Both human and murine models, the resistance to PCM is been associated with a Type I immunological response with high levels o IFN-³ and TNF-±, which would be associated with organized granuloma formation and fungal contention.Once the most likely route of infection is the conidia inhalation, in which in the lungs develop in the yeast pathogenic form, it is logical to presume that the pulmonary innate immunity, beyond being the main infection control mechanism on first contact with the fungus, it is responsible by later acquired immunity development. This way, several works presented the importance of macrophages, neutrophils and NK cels in P. brasiliensis resistance. However, little is known about the role of non-conventional cell population like invariant "Natural Killer" T cells (iNKT) and B-1 cells, in the immune response towards this pathogenUntil the present moment, it been demonstrated that B- cells can contribute to fungal infection by IL-10 secretion, while preliminary data from our laboratory indicates that the absence of iNKT cells its been associated to the susceptibility to P. brasiliensis.Since iNKT cells has been described as modulators of B-1 limphocytes activation, we intend to study the interaction between this two cell population in P. brasiliensis infection and the patology associated to PCM. Moreover, we Will study the effect of specific iNKT synthetic agonists in this interaction, consequently inPCM development.