Innate Immune Receptors and Defense Against Primary Pathogenic Fungi

Kirkland, Theo N.; Fierer, Joshua

doi:10.3390/vaccines8020303

Cited by 13 publications

(10 citation statements)

References 117 publications

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“…The major pattern recognition receptors (PRRs) involved with the recognition of fungi are Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) (Kirkland & Fierer, 2020). PPRs are expressed in many cell types involved in the innate immune response, and, upon activation, they trigger downstream signalling transduction pathways that lead to phagocytosis, microbial killing and cytokine production.…”

Section: Lipid Rafts and The Innate Immune Response To Fungal Infectionsmentioning

confidence: 99%

Host cell membrane microdomains and fungal infection

Souza

Valdez

Rizzo

et al. 2021

Cellular Microbiology

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Lipid microdomains or lipid rafts are dynamic and tightly ordered regions of the plasma membrane. In mammalian cells, they are enriched in cholesterol, glycosphingolipids, Glycosylphosphatidylinositol-anchored and signalling-related proteins. Several studies have suggested that mammalian pattern recognition receptors are concentrated or recruited to lipid domains during host-pathogen association to enhance the effectiveness of host effector processes. However, pathogens have also evolved strategies to exploit these domains to invade cells and survive. In fungal organisms, a complex cell wall network usually mediates the first contact with the host cells. This cell wall may contain virulence factors that interfere with the host membrane microdomains dynamics, potentially impacting the infection outcome. Indeed, the microdomain disruption can dampen fungus-host cell adhesion, phagocytosis and cellular immune responses. Here, we provide an overview of regulatory strategies employed by pathogenic fungi to engage with and potentially subvert the lipid microdomains of host cells. Take Away• Lipid microdomains are ordered regions of the plasma membrane enriched in cholesterol, glycosphingolipids (GSL), GPI-anchored and signalling-related proteins.• Pathogen recognition by host immune cells can involve lipid microdomain participation. During this process, these domains can coalesce in larger complexes recruiting receptors and signalling proteins, significantly increasing their signalling abilities.• The antifungal innate immune response is mediated by the engagement of pathogen-associated molecular patterns to pattern recognition receptors (PRRs) at the plasma membrane of innate immune cells. Lipid microdomains can concentrate or recruit PRRs during host cell-fungi association through a multi-interactive mechanism. This association can enhance the effectiveness of host effector processes. However, virulence factors at the fungal cell surface and extracellular vesicles can re-assembly these domains, compromising the downstream signalling and favouring the disease development.• Lipid microdomains are therefore very attractive targets for novel drugs to combat fungal infections.

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Section: Lipid Rafts and The Innate Immune Response To Fungal Infectionsmentioning

confidence: 99%

Host cell membrane microdomains and fungal infection

Souza

Valdez

Rizzo

et al. 2021

Cellular Microbiology

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“…Binding of these ligands via these pattern recognition receptors (PRRs) provide initial frontline defence and subsequent downstream modulation upon contact with micro-organisms [ 22 ]. Currently, there are more PRRs for fungi than any other type of organisms [ 23 ]. Previously, we and others have shown a number of CLRs important for host immune response to Pneumocystis .…”

Section: Discussionmentioning

confidence: 99%

Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein

Kottom

Carmona

Schaefbauer

et al. 2021

Journal of Medical Microbiology

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Introduction. Pathogen-associated molecular patterns’ (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses. Gap statement. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against Pneumocystis murina and Pneumocystis carinii and their purified major surface glycoproteins (Msgs). Aim. To study the potential of newly synthesized hFc-CLR fusions on binding to Pneumocystis and its Msg. Methods. A library of new synthesized hFc-CLR fusions was screened against Pneumocystis murina and Pneumocystis carinii organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model. Results. We detected a number of the CLR hFc-fusions displayed significant binding with P. murina and P. carinii organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (Mgl-1), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection. Conclusion. The data herein add to the growing list of CLRs recognizing Pneumocystis and provide insights for further study of organism/host immune cell interactions.

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“…The profound role of the host immune system to fight against fungal pathogens has been extensively described. Generally, two mainly types of immune cells, related to innate and adaptive immunity, dynamically contribute to effective immunity to eliminate the fungal pathogens [ 114 , 115 ].…”

Section: Role Of Immune Response Against the Most Clinically Relevant Fungal Infections In Covid-19 Patients: Two Sides Of A Coinmentioning

confidence: 99%

Overview on the Prevalence of Fungal Infections, Immune Response, and Microbiome Role in COVID-19 Patients

Roudbary

Kumar

et al. 2021

JoF

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Patients with severe COVID-19, such as individuals in intensive care units (ICU), are exceptionally susceptible to bacterial and fungal infections. The most prevalent fungal infections are aspergillosis and candidemia. Nonetheless, other fungal species (for instance, Histoplasma spp., Rhizopus spp., Mucor spp., Cryptococcus spp.) have recently been increasingly linked to opportunistic fungal diseases in COVID-19 patients. These fungal co-infections are described with rising incidence, severe illness, and death that is associated with host immune response. Awareness of the high risks of the occurrence of fungal co-infections is crucial to downgrade any arrear in diagnosis and treatment to support the prevention of severe illness and death directly related to these infections. This review analyses the fungal infections, treatments, outcome, and immune response, considering the possible role of the microbiome in these patients. The search was performed in Medline (PubMed), using the words “fungal infections COVID-19”, between 2020–2021.

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Innate Immune Receptors and Defense Against Primary Pathogenic Fungi

Cited by 13 publications

References 117 publications

Host cell membrane microdomains and fungal infection

Host cell membrane microdomains and fungal infection

Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein

Overview on the Prevalence of Fungal Infections, Immune Response, and Microbiome Role in COVID-19 Patients

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