Steryl Glycosides in Fungal Pathogenesis: An Understudied Immunomodulatory Adjuvant

Invasive fungal infections pose an increasing threat to human hosts, especially in immunocompromised individuals. In response to the increasing morbidity and mortality of fungal infections, numerous groups have shown great strides in uncovering novel treatment options and potential efficacious vaccine candidates for this increasing threat due to the increase in current antifungal resistance. Steryl glycosides are lipid compounds produced by a wide range of organisms, and are largely understudied in the field of pathogenicity, especially to fungal infections. Published works over the years have shown these compounds positively modulating the host immune response. Recent advances, most notably from our lab, have strongly indicated that steryl glycosides have high efficacy in protecting the host against lethal Cryptococcal infection through acting as an immunoadjuvant. This review will summarize the keystone studies on the role of steryl glycosides in the host immune response, as well as elucidate the remaining unknown characteristics and future perspectives of these compounds for the host–fungal interactions.

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Killing filarial nematode parasites: role of treatment options and host immune response

Infectious Diseases of Poverty ◽

10.1186/s40249-016-0183-0 ◽

2016 ◽

Vol 5 (1) ◽

Cited By ~ 15

Author(s):

Alexander Kwarteng ◽

Samuel Terkper Ahuno ◽

Freda Osei Akoto

Keyword(s):

Immune Response ◽

Treatment Options ◽

Host Immune Response ◽

Filarial Nematode ◽

Nematode Parasites

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Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor

Cancers ◽

10.3390/cancers13061443 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1443

Author(s):

Leonie D. H. Gossel ◽

Catrin Heim ◽

Lisa-Marie Pfeffermann ◽

Laura M. Moser ◽

Halvard B. Bönig ◽

...

Keyword(s):

High Risk ◽

Tumor Cells ◽

Chimeric Antigen Receptor ◽

Treatment Options ◽

Antigen Receptor ◽

Proof Of Concept ◽

Cell Monolayers ◽

Novel Treatment ◽

Dismal Prognosis

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.

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Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

Journal of Fungi ◽

10.3390/jof7020124 ◽

2021 ◽

Vol 7 (2) ◽

pp. 124

Author(s):

Charmaine Retanal ◽

Brianna Ball ◽

Jennifer Geddes-McAlister

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Treatment Options ◽

Global Scale ◽

Host Cells ◽

Candida Spp ◽

Post Translational Modifications ◽

Fungal Host ◽

Resistant Species

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.

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The possible role of the frontal and sub-parietal gland systems of the pentastomidReighardia sternae(Diesing, 1864) in the evasion of the host immune response

Parasitology ◽

10.1017/s0031182000048587 ◽

1979 ◽

Vol 78 (1) ◽

pp. 53-66 ◽

Cited By ~ 19

Author(s):

J. Riley ◽

J. L. James ◽

A. A. Banaja

Keyword(s):

Immune Response ◽

Alternative Explanation ◽

Surface Membrane ◽

Membrane System ◽

Host Immune Response ◽

Entire Surface ◽

Strong Immune Response ◽

Concomitant Immunity ◽

Host Parasite

SUMMARYThe frontal and sub-parietal glands of the pentastomidReighardia sternaeelaborate lamellate secretion which is poured on to the cuticle. The entire surface of the cuticle, including the mouth, hook pits and reproductive apertures, is coated with secretion. Electron microscope studies indicate that the glands are continuously active, which implies a turnover of surface membranes. The postulated function of these membranes is to protect certain vital areas of the host–parasite interface, notably the pores of ion-transporting cells, from the host immune response. The available evidence suggests that pentastomids do evoke a strong immune response but since most are long-lived they must circumvent it. We believe the surface membrane system to be instrumental in this. Studies on another pentastomid,Porocephalus crotaliin rats have shown that an immune response stimulated by a primary infection will kill subsequent infections and that the surface membranes are strongly immunogenic. Obvious parallels between this situation and that of schistosome infections in mammals are discussed. An alternative explanation of concomitant immunity is proposed.

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

Journal of Fungi ◽

10.3390/jof7090720 ◽

2021 ◽

Vol 7 (9) ◽

pp. 720

Author(s):

Maryam Roudbary ◽

Sunil Kumar ◽

Awanish Kumar ◽

Lucia Černáková ◽

Fatemeh Nikoomanesh ◽

...

Keyword(s):

Immune Response ◽

Intensive Care ◽

Intensive Care Units ◽

Fungal Infections ◽

Fungal Species ◽

Fungal Diseases ◽

Severe Illness ◽

Rising Incidence ◽

Cryptococcus Spp

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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Immunity and its role in periodontal diseases

Romanian Journal of Stomatology ◽

10.37897/rjs.2017.1.4 ◽

2017 ◽

Vol 63 (1) ◽

pp. 24-27

Author(s):

Irina Dumitrache ◽

Keyword(s):

Immune Response ◽

Chronic Disease ◽

Periodontal Disease ◽

Clinical Efficacy ◽

Periodontal Diseases ◽

Adult Population ◽

Host Immune Response ◽

Immunomodulatory Therapy ◽

Common Chronic Disease

Periodontal disease is one of the most common chronic disease, with a prevalence between 5% and 30% in adult population aged 25-75. In the pathogenesis of periodontal disease, the host immune response has a great importance and in the last years it has been underlined the role of immunomodulatory therapy in the management of periodontal disease. Septilin is a herbal immunomodulatory with clinical efficacy proven in the periodontal disease.

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Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients

PLoS ONE ◽

10.1371/journal.pone.0013099 ◽

2010 ◽

Vol 5 (10) ◽

pp. e13099 ◽

Cited By ~ 54

Author(s):

Vidya A. Arankalle ◽

Kavita S. Lole ◽

Ravi P. Arya ◽

Anuradha S. Tripathy ◽

Ashwini Y. Ramdasi ◽

...

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Viral Load ◽

Virus Infection ◽

Influenza Virus Infection ◽

Host Immune Response ◽

Pandemic H1n1 ◽

Differential Outcome ◽

Pandemic H1n1 2009

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Role of DNA repair in host immune response and inflammation

Mutation Research/Reviews in Mutation Research ◽

10.1016/j.mrrev.2014.11.004 ◽

2015 ◽

Vol 763 ◽

pp. 246-257 ◽

Cited By ~ 15

Author(s):

Fabrícia Lima Fontes ◽

Daniele Maria Lopes Pinheiro ◽

Ana Helena Sales de Oliveira ◽

Rayssa Karla de Medeiros Oliveira ◽

Tirzah Braz Petta Lajus ◽

...

Keyword(s):

Immune Response ◽

Dna Repair ◽

Host Immune Response

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Review on the Role of Host Immune Response in Protection and Immunopathogenesis during Cutaneous Leishmaniasis Infection

Journal of Immunology Research ◽

10.1155/2020/2496713 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Teshager Dubie ◽

Yasin Mohammed

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Proinflammatory Cytokines ◽

Parasitic Infection ◽

Host Immune Response ◽

Immune Defense ◽

Host Cells ◽

Infected Host ◽

Major Public Health Problem

Cutaneous leishmaniasis (CL) is a major public health problem worldwide and spreads to human via the bite of sand flies during blood meal. Following its inoculation, the promastigotes are immediately taken up by phagocytic cells and these leishmania-infected host cells produce proinflammatory cytokines that activate other immune cells and these infected host cells produce more cytokines and reactive nitrogen and oxygen species for efficient control of leishmania infection. Many experimental studies showed that resistance to infection with leishmania paraites is associated with the production of proinflammatory cytokines and activation of CD4+ Th1 response. On the other hand, vulnerability to this parasitic infection is correlated to production of T helper 2 cytokines that facilitate persistence of parasites and disease progression. In addition, some studies have also indicated that CD8+ T cells play a vital role in immune defense through cytokine production and their cytotoxic activity and excessive production of proinflammatory mediators promote amplified recruitment of cells. This could be correlated with excessive inflammatory reaction and ultimately resulted in tissue destruction and development of immunopathogenesis. Thus, there are contradictions regarding the role of immune responses in protection and immunopathogenesis of CL disease. Therefore, the aim of this paper was to review the role of host immune response in protection and its contribution to disease severity for CL infection. In order to obtain more meaningful data regarding the nature of immune response to leishmania, further in-depth studies focused on immune modulation should be conducted to develop better therapeutic strategies.

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