Abstract
The incidence of fungal infections has dramatically increased in recent years, in large part due to increased use of immunosuppressive medications, as well as aggressive medical and surgical interventions that compromise natural skin and mucosal barriers. There are relatively few currently licensed antifungal drugs, and rising resistance to these agents has led to interest in the development of novel preventative and therapeutic strategies targeting these devastating infections. One approach to combat fungal infections is to augment the host immune response towards these organisms. The polysaccharide-rich cell wall is the initial point of contact between fungi and the host immune system, and therefore, represents an important target for immunotherapeutic approaches. This review highlights the advances made in our understanding of the mechanisms by which the immune system recognizes and interacts with exopolysaccharides produced by four of the most common fungal pathogens: Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, and Histoplasma capsulatum. Work to date suggests that inner cell wall polysaccharides that play an important structural role are the most conserved across diverse members of the fungal kingdom, and elicit the strongest innate immune responses. The immune system senses these carbohydrates through receptors, such as lectins and complement proteins. In contrast, a greater diversity of polysaccharides is found within the outer cell walls of pathogenic fungi. These glycans play an important role in immune evasion, and can even induce anti-inflammatory host responses. Further study of the complex interactions between the host immune system and the fungal polysaccharides will be necessary to develop more effective therapeutic strategies, as well as to explore the use of immunosuppressive polysaccharides as therapeutic agents to modulate inflammation.
Highlights
Over the past several decades, there has been a marked increase in the use of immunosuppressive therapy for the treatment of haematologic malignancies, stem cell and solid organ transplantation, and rheumatologic disorders
This signalling occurred via TLR2 activation in macrophages, and may provide a mechanism for the host to discriminate between pathogenic C. albicans and the commensal Saccharomyces cerevisiae, which lacks these β-(1,2)-mannan sidechains [18]
The mannose-binding lectin (MBL)-pentraxin-3 heterocomplex activates complement-mediated killing through deposition of complement protein C1q [60]. These findings suggest that MBL mediates a complex anti-C. albicans response through both complement-mediated killing and opsonisation
Summary
Over the past several decades, there has been a marked increase in the use of immunosuppressive therapy for the treatment of haematologic malignancies, stem cell and solid organ transplantation, and rheumatologic disorders. There has been an increased use of novel surgical techniques, indwelling central venous catheters, and other prosthetic devices in hospitalized patients These changes in health care, combined with the HIV epidemic, have resulted in a rapid expansion in the number of patients with acquired defects in innate, acquired, and mucosal immunity. We have focussed our attention four of the our current understanding of the immune response to fungal exopolysaccharides, and the on molecular most common medically relevant fungi: Candida fumigatus, mechanisms underlying the recognition of thesealbicans, glycans.Aspergillus. Strongest host immune responses through interactions with soluble and cell-associated pattern medically relevant fungi have developed unique exopolysaccharides that often serve to mask the recognition receptors.
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