Host Response to Pulmonary Fungal Infections: a Highlight on Cell-Driven Immunity to Cryptococcus Species and Aspergillus fumigatus

Purpose of Review In this article, we provide a summary of recent findings in the field of host responses to fungal infections caused by the environmental fungi Aspergillus fumigatus and Cryptococcus species. Key myeloid and lymphoid cells that are important in antifungal responses are discussed. The primary leukocytes discussed are macrophages, monocytes, dendritic cells, neutrophils, natural killer cells, and T cells, all of which play roles in conferring protective immunity to these opportunistic pathogens. Recent Findings An immunocompromised status is the primary risk factor for Aspergillus - and Cryptococcus -induced morbidities and mortalities, despite the use of current antifungal therapeutics. Research in the past several years has revealed that a variety of immune cell types play critical roles in mounting protection in healthy individuals. The essential effector responses involved in anti- Aspergillus and anti- Cryptococcus immunities differ in several aspects, despite the fact that both are fungi that in humans primarily colonize the pulmonary tissue. Alveolar macrophages and neutrophils comprise the first line of defense that engulfs and eliminates fungi, primarily through the release of free radicals. Monocytes and dendritic cells are the immune sentinels that not only directly eliminate fungi, but also modulate the functions of other immune cells and activate fungus-specific T cells. Summary Increased prevalence of immunosuppressive drugs and incidence of diseases such as HIV/AIDS have led to greater numbers of immune-incompetent hosts who are at risk for fatally invasive Aspergillus or Cyrptococcus infections. Elucidating the mechanisms and key immune effectors that combat these infections is crucial for the development of future therapies.