Immune defence to invasive fungal infections: A comprehensive review

Pathakumari, Balaji; Liang, Guanzhao; Liu, Weida

doi:10.1016/j.biopha.2020.110550

Cited by 155 publications

(140 citation statements)

References 236 publications

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“…Chemokines produced by neutrophils are involved in the chemotaxis for the rapid migration of immune cells to the infection site. Neutrophils granules contain antimicrobial peptides, nucleolytic enzymes, and also oxygen metabolites acting in the removal process disrupting the cell membrane of fungus (Traynor and Huffnagle, 2001;Rodrigues et al, 2007;Gonzaĺez et al, 2008b;Pathakumari et al, 2020). In addition, PMNs are able to produce extracellular traps (NETs), these structures are able to capture microbials, degrade their virulence factors, and eliminate the pathogens (Mejıá et al, 2015;Restrepo et al, 2015).…”

Section: Polymorphonuclear Neutrophilsmentioning

confidence: 99%

The Trojan Horse Model in Paracoccidioides: A Fantastic Pathway to Survive Infecting Human Cells

Giusiano

2021

Front. Cell. Infect. Microbiol.

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Paracoccidioidomycosis (PCM) is the most relevant systemic endemic mycosis limited to Latin American countries. The etiological agents are thermally dimorphic species of the genus Paracoccidioides. Infection occurs via respiratory tract by inhalation of propagules from the environmental (saprophytic) phase. In the lung alveoli the fungus converts to the characteristic yeast phase (parasitic) where interact with extracellular matrix proteins, epithelial cells, and the host cellular immunity. The response involves phagocytic cells recognition but intracellular Paracoccidioides have demonstrated the ability to survive and also multiply inside the neutrophils, macrophages, giant cells, and dendritic cells. Persistence of Paracoccidioides as facultative intracellular pathogen is important in terms of the fungal load but also regarding to the possibility to disseminate penetrating other tissues even protected by the phagocytes. This strategy to invade other organs via transmigration of infected phagocytes is called Trojan horse mechanism and it was also described for other fungi and considered a factor of pathogenicity. This mini review comprises a literature revision of the spectrum of tools and mechanisms displayed by Paracoccidioides to overcame phagocytosis, discusses the Trojan horse model and the immunological context in proven models or the possibility that Paracoccidioides apply this tool for dissemination to other tissues.

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Section: Polymorphonuclear Neutrophilsmentioning

confidence: 99%

The Trojan Horse Model in Paracoccidioides: A Fantastic Pathway to Survive Infecting Human Cells

Giusiano

2021

Front. Cell. Infect. Microbiol.

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“…It might be hypothesized that stimulation of MCs with various doses of zymosan can result in differences in the affinity, avidity, or threshold of signaling via Dectin-1 and that this translates into qualitative changes in the signaling pathways with the involvement of interferon regulatory factor (IRF)3, which is crucial for IFN-β synthesis [ 33 ]. Emerging data highlight multidirectional role of studied cytokines/chemokines in the immune response against some fungal pathogens [ 34 , 35 ]. They are critical in mediating host cell-to-cell communication and promoting the initiation, maintenance, or resolution of the inflammatory processes during infection.…”

Section: Discussionmentioning

confidence: 99%

Native and IgE-primed rat peritoneal mast cells exert pro-inflammatory activity and migrate in response to yeast zymosan upon Dectin-1 engagement

et al. 2021

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Mast cells (MCs) play an essential role in host defense, primarily because of their location, their ability to pathogen destruction via several mechanisms, and the pattern recognition receptors they express. Even though most data is available regarding MC activation by various bacteria- or virus-derived molecules, those cells’ activity in response to constituents associated with fungi is not recognized enough. Our research aimed to address whether Saccharomyces cerevisiae-derived zymosan, i.e., β-(1,3)-glucan containing mannan particles, impacts MC activity aspects. Overall, the obtained results indicate that zymosan has the potential to elicit a pro-inflammatory response of rat peritoneal MCs. For the first time ever, we provided evidence that zymosan induces fully mature MC migration, even in the absence of extracellular matrix (ECM) proteins. Moreover, the zymosan-induced migratory response of MCs is almost entirely a result of directional migration, i.e., chemotaxis. We found that zymosan stimulates MCs to degranulate and generate lipid mediators (cysLTs), cytokines (IFN-α, IFN-β, IFN-γ, GM-CSF, TNF), and chemokine (CCL2). Zymosan also upregulated mRNA transcripts for several cytokines/chemokines with pro-inflammatory/immunoregulatory activity. Moreover, we documented that zymosan activates MCs to produce reactive oxygen species (ROS). Lastly, we established that the zymosan-induced MC response is mediated through activation of the Dectin-1 receptor. In general, our results strongly support the notion that MCs contribute to innate antifungal immunity and bring us closer to elucidate their role in host-pathogenic fungi interactions. Besides, provided findings on IgE-sensitized MCs appear to indicate that exposure to fungal zymosan could affect the severity of IgE-dependent disorders, including allergic ones.

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“…The balance between Th1 and Th2 subset determined the quality and outcome of host immune responses. It was also found that Th17 played multiple roles in clearing infections by participating in the production of proinflammatory genes and anti microbial peptides, recruitment, and activation of neutrophils (Pathakumari et al 2020). T cell immunity against fungal infections primes Th1 type response (Shenoy et al 2017).…”

Section: Adaptive Immunity Mechanismmentioning

confidence: 99%

The Pathogenesis of Aspergillus fumigatus, Host Defense Mechanisms, and the Development of AFMP4 Antigen as a Vaccine

Hua

Zhang³

et al. 2021

Polish Journal of Microbiology

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Aspergillus fumigatus is one of the ubiquitous fungi with airborne conidia, which accounts for most aspergillosis cases. In immunocompetent hosts, the inhaled conidia are rapidly eliminated. However, immunocompromised or immunodeficient hosts are particularly vulnerable to most Aspergillus infections and invasive aspergillosis (IA), with mortality from 50% to 95%. Despite the improvement of antifungal drugs over the last few decades, the therapeutic effect for IA patients is still limited and does not provide significant survival benefits. The drawbacks of antifungal drugs such as side effects, antifungal drug resistance, and the high cost of antifungal drugs highlight the importance of finding novel therapeutic and preventive approaches to fight against IA. In this article, we systemically addressed the pathogenic mechanisms, defense mechanisms against A. fumigatus, the immune response, molecular aspects of host evasion, and vaccines’ current development against aspergillosis, particularly those based on AFMP4 protein, which might be a promising antigen for the development of anti-A. fumigatus vaccines.

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Immune defence to invasive fungal infections: A comprehensive review

Cited by 155 publications

References 236 publications

The Trojan Horse Model in Paracoccidioides: A Fantastic Pathway to Survive Infecting Human Cells

The Trojan Horse Model in Paracoccidioides: A Fantastic Pathway to Survive Infecting Human Cells

Native and IgE-primed rat peritoneal mast cells exert pro-inflammatory activity and migrate in response to yeast zymosan upon Dectin-1 engagement

The Pathogenesis of Aspergillus fumigatus, Host Defense Mechanisms, and the Development of AFMP4 Antigen as a Vaccine

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