Classical versus alternative macrophage activation: the Ying and the Yang in host defense against pulmonary fungal infections

Macrophages are innate immune cells that possess unique abilities to polarize toward different phenotypes. Classically activated macrophages are known to have major roles in host defense against various microbial pathogens, including fungi, while alternatively activated macrophages are instrumental in immune-regulation and wound healing. Macrophages in the lungs are often the first responders to pulmonary fungal pathogens, and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. This review discusses the distinct macrophage polarization states and their roles during pulmonary fungal infection. We focus primarily on Cryptococcus neoformans and Pneumocystis model systems as disease resolution of these two opportunistic fungal pathogens is linked to classically or alternatively activated macrophages, respectively. Further research considering macrophage polarization states that result in anti-fungal activity has the potential to provide a novel approach for the treatment of fungal infections.