4  Lung surfactant as a barrier to cryptococcal infection
The inner surface of alveoli are covered in a film of surfactant that functions to ensure the alveoli in the lung are capable of full re-inflation, through maintenance of surface tension (Schurch et al., 1992). Surfactants are also known to play a role in the lung immune defence with particles deposited within the lung being pulled towards the alveoli wall by the surfactant promoting the interaction of pathogens and surfactant proteins (Schurch et al., 1992). Surfactant proteins SP-A and SP-D are members of the immune collectins. They bind to pathogens and promote macrophage and neutrophil immune function by opsonising pathogens and increasing phagocytosis (Kishore et al., 2005; Wright, 2004). Both SP-A and SP-D preferentially bind to pathogens over host cells through favoured binding to pathogen associated molecules e.g. mannose (Kishore et al., 2005).
SP-A and SP-D are known to bind viral, bacterial and fungal pathogens, including C. neoformans (Schelenz et al., 1995). SP-A and SP-D bind both acapsular and encapsulated C. neoformans but the effect of binding differs. SP-A bound to encapsulated yeast was not beneficial to the host, as a murine SP-A knockout model showed no difference in survival to wild type (Giles et al., 2007). This suggests that SP-A will have little effect once C. neoformans has induced capsule synthesis and may be one mechanism by which the cryptococcal capsule promotes virulence through blocking the action of SP-A. Similarly, SP-D can bind both acapsular and encapsulated yeast but there is only increased phagocytosis of acapsular yeast in vivo (Geunes-Boyer et al., 2009). There is evidence that SP-D promotes virulence of encapsulated C. neoformans as SP-D knock-out mice were better able to control cryptococcal infection than wild-type mice (Geunes-Boyer et al., 2012, 2009). Two possible explanations for this are that SP-D protects cryptococci from macrophage mediated degradation (so far only demonstrated in vitro) and that SP-D promotes the recruitment of eosinophils that may be detrimental to the control and clearance of pulmonary cryptococcosis (Holmer et al., 2014).