Pulmonary Macrophage and Dendritic Cell Responses to Cryptococcus neoformans

Abstract

The fungal pathogen Cryptococcus neoformans can cause life-threatening infections in immune compromised individuals. This pathogen is typically acquired via inhalation, and enters the respiratory tract. Innate immune cells such as macrophages and dendritic cells (DCs) are the first host cells that encounter C. neoformans, and the interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease. Cryptococcus possesses several virulence factors and evasion strategies to prevent its killing and destruction by pulmonary phagocytes, but these phagocytic cells can also contribute to anti-cryptococcal responses. This review will focus on the interactions between Cryptococcus and primary macrophages and dendritic cells (DCs), dealing specifically with the cryptococcal/pulmonary cell interface.

Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection

“…In addition to the airway epithelial cells, CD11c + airway resident immune cells such as alveolar macrophages (AM) and DCs have been reported to be the dominant cell populations in uninfected lungs ( 47 , 136 – 139 ) and have been arguably the most widely studied cell population in the cryptococcal literature ( Figure 1 ). These cells are found ubiquitously in the lower respiratory and alveolar spaces of the airway lumen and the underlying lamina propria below the epithelium.…”

“…Lung resident DCs express CD11c and MHC-II markers and have been highly implicated in early defense against invading pathogens and have gained an increased appreciation in antifungal immunology over the last decade. DCs are innate phagocytes with a central role to bridge the innate and adaptive arms of the immune systems upon initial infection with a pathogen, including C. neoformans ( 47 , 170 ). Phagocytosis of the yeast requires complement or antibody-mediated opsonization of the GXM capsule ( 116 , 171 ), and the DCs kill C. neoformans through lysosomal degradation ( 47 ).…”

“…DCs are innate phagocytes with a central role to bridge the innate and adaptive arms of the immune systems upon initial infection with a pathogen, including C. neoformans ( 47 , 170 ). Phagocytosis of the yeast requires complement or antibody-mediated opsonization of the GXM capsule ( 116 , 171 ), and the DCs kill C. neoformans through lysosomal degradation ( 47 ). Concurrently, DCs will upregulate co-stimulatory molecules such as CD80 and CD86 for antigen presentation to T cells.…”

“…DCs are a diverse cell type with several subsets each possessing specialized functions and regarded as essential components of antifungal immunity including against C. neoformans . Three main subsets can be found within the lungs: CD103+ classic DCs (cDC1), CD11b+ cDC (cDC2), and plasmacytoid DCs (pDC) ( 47 , 116 , 172 ).…”

“…Recruited inflammatory DCs are monocyte-derived and termed monocyte-derived DCs (moDCs) ( 110 , 116 , 219 ). Overall, moDCs differ from resident DCs in phagocytosis and killing, cytokine release, and migration from the periphery to the nearest draining lymph nodes for activation of adaptive cell-mediated immunity ( 47 , 198 , 220 – 225 ). Upon arrival in the lung, moDCs downregulate the monocytic marker Ly6C and possess overlapping function with cDCs.…”