Immunity to Commensal Fungi: Detente and Disease

Abstract

Fungi are ubiquitous in our environment, and a healthy immune system is essential to maintain adequate protection from fungal infections. When this protection breaks down, superficial and invasive fungal infections cause diseases that range from irritating to life-threatening. Millions of people worldwide develop invasive infections during their lives, and mortality for these infections often exceeds 50%. Nevertheless, we are normally colonized with many of the same disease-causing fungi (e.g., on the skin or in the gut). Recent research is dramatically expanding our understanding of the mechanisms by which our immune systems interact with these organisms in health and disease. In this review, we discuss what is currently known about where and how the immune system interacts with common fungi.

<p>Dendritic Cells Promote Treg Expansion but Not Th17 Generation in Response to <em>Talaromyces marneffei</em> Yeast Cells</p>

“…On the basis of previous studies, 2,7,28 we predicted that increased inflammatory effector T cells (such as Th1 and Th17) and M1 macrophages activation in response to T. marneffei are beneficial for pathogen elimination. Given that Th17 is critical for host defense in fungal infections, [17][18][19]21,22 the immune cell pattern switching to a tolerogenic phenotype may be harmful for the defense against T. marneffei. The sustained expression of IL-10 is associated with the persistence of many fungal or parasite infections.…”

“…15,16 Indeed, a prominent Th17 immune response is effective against infections with Candida, [17][18][19] Aspergillus fumigatus, 20 C. neoformans, 21 and other fungal pathogens. 11,22 In addition, besides the loss of IFN-γ production, impaired production of interleukin (IL)-17A by lymphocytes was also evident in patients with systemic penicilliosis harboring gain-of-phosphorylation signal transducer and activator of transcription (STAT) 1 mutations. 7 Based on these findings, it is possible that the Th17 immune response protects against T. marneffei.…”

Host–microbe interactions: commensal fungi in the gut

“…Growing evidence documents that the mammalian gut is home to a diverse population of fungi that co-exist with other microbes in the intestinal microbiome including bacteria and viruses [1] (Fig. 1).…”

Antifungal Innate Immunity: A Perspective from the Last 10 Years

“…Th1-type cytokines stimulate the effector function of phagocytes, while Th17-related cytokines, such as IL-17 and IL-22, promote the release of antimicrobial peptides by mucosal epithelial cells and induce neutrophil recruitment and activation [6, 17, 84-86]. The role of other adaptive immune cells, such as B cells, is less clear and has been reviewed elsewhere [23, 87]. Here, we are going to focus on recent advances in our understanding of the pivotal role of innate immune cells, including granulocytes, monocytes, macrophages, DCs, and innate lymphoid cells, in antifungal immunity (Fig.…”

“…Their importance in fungal infections was originally demonstrated in humans suffering from neutropenia that exhibited a dramatic increase in susceptibility to major fungal pathogens, including C. albicans and A. fumigatus. Moreover, mutations associated with various aspects of neutrophil recruitment and antimicrobial activity, including CXCR1, NADPH oxidase, and myeloperoxidase, are strongly associated with an increased risk of systemic fungal infections in humans [87]. Neutrophils use oxidative and nonoxidative killing mechanisms against fungal pathogens (Fig.…”