It takes a village: Phagocytes play a central role in fungal immunity

Abstract

Phagocytosis is an essential step in the innate immune response to invasive fungal infections. This process is carried out by a proverbial "village" of professional phagocytic cells, which have evolved efficient machinery to recognize and ingest pathogens, namely macrophages, neutrophils and dendritic cells. These innate immune cells drive early cytokine production, fungicidal activity, antigen presentation and activation of the adaptive immune system. Despite the development of antifungal agents with potent activity, the biological activity of professional phagocytic innate immune cells has proven indispensable in protecting a host from invasive fungal infections. Additionally, an emerging body of evidence suggests non-professional phagocytes, such as airway epithelial cells, carry out phagocytosis and may play a critical role in the elimination of fungal pathogens. Here, we review recent advances of phagocytosis by both professional and non-professional phagocytes in response to fungal pathogens, with a focus on invasive aspergillosis as a model disease.

HDAC11 negatively regulates antifungal immunity by inhibiting Nos2 expression via binding with transcriptional repressor STAT3

“…5C and D ). Phagocytosis is also a key process in the antifungal response [ 34 ]. However, Hdac11 deletion did not alter phagocytic activity as compared to Hdac11 +/+ cells ( Fig.…”

The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis

“…In contrast to several pathogenic fungi that avoid intracellular killing by lysing the host’s cells ( 28 , 40 ), L. corymbifera did not cause significant damage in phagocytic monocytes ( Figure 1F ) and did not impair their viability over 24 hours of infection ( Figure S3B ), which was unexpected considering that several clinical cases of mucormycosis reported rapid destruction of tissue and necrosis, as well as the epithelial and endothelial damage caused by other mucoralean fungi upon intracellular growth ( 1 , 6 , 30 , 61 , 62 ). Moreover, L. corymbifera spores did not exhibit intracellular germination and remained alive after 24 hours of phagocytosis by human monocytes ( Figures 1D, E, G ), suggesting that the fungus inhibits the intracellular enzymatic degradation, which occurs in the phagolysosome after activation of specific PRRs and recruitment of specific phagosome proteins ( 28 , 63 ).…”

The Known Unknowns of the Immune Response to Coccidioides

“…Airway epithelium is an immunologically active tissue that may participate in pathogen phagocytosis [ 67 , 68 ] yet these data are hard to interpret as immortalized cell lines show significant capacity to phagocytose, a feature not seen in primary airway epithelium. Although resident alveolar macrophages and DCs play a role in initial host responses, it is increasingly evident that airway epithelial cells are essential in coordination of immune cell recruitment in the presence of inhaled pathogens in immunocompetent individuals [ 69 ].…”