Abstract

Invariant NKT cells (iNKT cells) are a subset of T cells that co express NK receptors and a restricted TCR and recognize glycolipids antigens presented by the CD1d. Once activated, these cellas are able to produce large amounts of both Th1 and Th2 cytokines, which endow them to play a pivotal role at the interface between innate and adaptative immune responses. These cells are also involved in granuloma formation and deficiency in iNKT cells number or function has been partially implicated in susceptibility to some infectious diseases, such as tuberculosis. However, no studied adressed the role of iNKT cells in a human fungus disease, such as paracoccidioidomycosis (PCM). We evaluated iNKT cells in healthy individuals who have had PCM, representing susceptible individuals, and compared this group with healthy individuals who have or have not been exposed to the fungus but never developed PCM. iNKT cells were detected using PBS57-loaded tetramer staining and flow cytometry. Circulating iNKT cell numbers were similar among healthy individuals who had previously been cured of paracoccidioidomycosis (susceptible individuals, n=7) and healthy Paracoccidioides brasiliensis-infected (n=5) and non-infected individuals (n=5). iNKT from all three groups expanded similarly upon α-GalCer and a synthetic analog (OCH) stimulation. IFN-γ was the dominant cytokine produced both by ex vivo and expanded iNKT cells, followed by IL-4 and IL-10, in the three groups. No deficit in monocyte-expression of CD1d was detected. In conclusion, individuals who had developed paracoccidioidomycosis in the past have no impairment in iNKT number, expansion capacity and cytokine secretion. ਀ Financial suport: Fundação de Amparo à Pesquisa de São Paulo - Fapesp. Grant# 07/58598-8 and 07/58462-9਀㰀⼀昀漀渀琀㸀㰀⼀瀀㸀㰀戀爀㸀㰀戀㸀䬀攀礀眀漀爀搀㨀 㰀⼀戀㸀☀渀戀猀瀀㬀一䬀吀 挀攀氀氀猀Ⰰ 倀愀爀愀挀漀挀挀椀搀椀漀椀搀漀洀礀挀漀猀椀猀Ⰰ 挀礀琀漀欀椀渀攀猀㰀⼀琀搀㸀㰀⼀琀爀㸀㰀⼀琀愀戀氀攀㸀㰀⼀琀爀㸀㰀⼀琀搀㸀㰀⼀琀愀戀氀攀㸀㰀⼀戀漀搀礀㸀㰀⼀栀琀洀氀㸀