In addition to CD4+ and CD8+ T cells, there are lymphocytes that can be considered acting as part of the innate immune system involved in the host response to C. neoformans: natural killer cells, natural killer T cells, and γδ T cells. Firstly, natural killer cells (NKs) are able release granules, but unlike CD8+ cells, utilise perforin rather than granulysin, through a PI3K-ERK1/2 dependent pathway to cause cryptococcal degradation (Ma et al., 2004; Wiseman et al., 2007). After degranulation the NK cells are still able to continue anti cryptococcal activities, due to constitutive expression of perforin and granulysin, and rearming of NK cells through direct contact with cryptococcal cells (Ma et al., 2004; Marr et al., 2009). Recently, NK cells have also been shown to be key in the immune response to cryptococcal granulomas, having an ability to continue anti fungal degranulation despite an acidic environment (Islam et al., 2013). NK cells are thus important in the clearance of cryptococcal cells and granulomas. Natural killer T cells (NKT) are also able to combat cryptococcal infection. NKT cells are recruited to mouse lungs after infection, and are able to produce IFNγ in response to cryptococcal challenge, resulting in a Th1 profile beneficial for the host to stop cryptococcal infection (Kawakami et al., 2001a,b). In contrast, γδ T cells do not promote fungal clearance in the host response to C. neoformans, indicated by mice deficient in γδ T cells that were able to control the fungal infection better than controls, due to a change towards a Th1 profile (Uezu et al., 2004).