Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis .

Invariant Natural Killer T (iNKT) cells are key players in the immunity to several pathogens; however, their involvement in the resistance to Paracoccidioides brasiliensis infection remains unknown. Using splenocytes from CD1d (CD1d ^-/- ) and iNKT-deficient (J α 18 ^-/- ) mice, we found that iNKT cells are the innate source of IFN- γ after P. brasiliensis infection and are required to potentiate macrophage oxidative burst and control fungal growth. To determine whether iNKT cells contribute in vivo to host resistance against P. brasiliensis infection, we infected intratracheally wild-type and J α 18 ^-/- C57BL/6 mouse strains with the virulent Pb18 isolate. iNKT cell deficiency impaired the airway acute inflammatory response, resulting in decreased airway neutrophilia and reduced IFN- γ , KC, and nitric oxide (NO) production. The deficient innate immune response of J α 18 ^-/- mice to Pb18 infection resulted in increased fungal burden in the lungs and spleen. Besides, the activation of iNKT cells in vivo by administration of the exogenous iNKT ligand α -galactosylceramide ( α -GalCer) improved host resistance to P. brasiliensis infection. Although the mechanisms responsible for this phenomenon remain to be clarified, α -GalCer treatment boosted the local inflammatory response and reduced pulmonary fungal burden. In conclusion, our study is the first evidence that iNKT cells are important for the protective immunity to P. brasiliensis infection and their activation by an exogenous ligand is sufficient to improve the host resistance to this fungal infection.
Competing Interests: Although ACK is a member of the academic editorial board from the Journal of Immunology Research, he declares no conflict of interest. All the other authors declare that there is no conflict of interest.
(Copyright © 2021 Joes Nogueira-Neto et al.)