Systemic Th2 polarization and local Th1 response retention in the CNS confirmed the “Th1 protective immunity” theory proposed by Kawakami et al., indicating that the Th1 immune response (marked by IFN-γ, IL-12, and TNF-α) plays a key role in the control of cryptococcal infection, whereas the Th2 response (marked by IL-4 and IL-13) may aggravate infection by inhibiting macrophage activity (Kawakami et al., 1996). Here, TNF is linked to cryptococcosis.