Role of Dectin-2 in the Phagocytosis of Cryptococcus neoformans by Dendritic Cells

Kitai, Yuki; Sato, Ko; Tanno, Daiki; Yuan, Xiaoliang; Umeki, Aya; Kasamatsu, Jun; Emi, Kazuyuki; Tanno, Hiromasa; Hara, Hiromitsu; Yamasaki, Satoshi; Saijo, Shinobu; Iwakura, Yoichiro; Kawakami, Kazuyoshi

doi:10.1128/iai.00330-21

Cited by 19 publications

(18 citation statements)

References 38 publications

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“…The pathogenic Cryptococcus enters the human host via inhalation into the lung, where the environment is limiting in serum opsonin and the mechanism of nonopsonic phagocytosis occurs via phagocytes in such situations [ 40 ]. In addition, the cell walls and capsules of Cryptococcus are rich in immunomodulatory polysaccharides of glucuronoxylomannan, which is shed from the fungus and circulates in the blood and cerebrospinal fluid of patients with cryptococcosis [ 41 ]. The uptake of nonopsonized Cryptococcus neoformans (via both dectin-1 and dectin-2) and Cryptococcus gattii (largely via dectin-1) through the mannose receptor is dependent on macrophage activation by cytokines.…”

Section: Pathogenesismentioning

confidence: 99%

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic

Chan

Lai

et al. 2022

JoF

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or secondary infection among patients with COVID-19. The possible co-pathogens include bacteria, viruses, and fungi, but COVID-19-associated cryptococcosis is rarely reported. This review provided updated and comprehensive information about this rare clinical entity of COVID-19-associated cryptococcosis. Through an updated literature search till 23 August 2022, we identified a total of 18 culture-confirmed case reports with detailed information. Half (n = 9) of them were elderly. Fifteen (83.3%) of them had severe COVID-19 and ever received systemic corticosteroid. Disseminated infection with cryptococcemia was the most common type of cryptococcosis, followed by pulmonary and meningitis. Except one case of C. laurentii, all other cases are by C. neoformans. Liposomal amphotericin B and fluconazole were the most commonly used antifungal agents. The overall mortality was 61.1% (11/18) and four of them did not receive antifungal agents before death. Improving the poor outcome requires a physician’s high suspicion, early diagnosis, and prompt treatment.

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Section: Pathogenesismentioning

confidence: 99%

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic

Chan

Lai

et al. 2022

JoF

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“…We cannot exclude the possibility that other phagocytic receptors may contribute to epithelial phagocytosis of C. albicans , hence, we asked whether such receptors are expressed by IECs. To this end, we tested Dectin-2/CLEC6A, which is implicated in fungal phagocytosis (Ifrim et al, 2016; Kitai et al, 2021; Lamprinaki et al, 2017). Indeed, we detected Dectin-2 on the surface of human ileal and colonic IECs isolated from surgical specimens by flow cytometry (Supp.…”

Section: Resultsmentioning

confidence: 99%

Human intestinal epithelial cells can internalize luminal fungi via LC3-associated phagocytosis

Cohen-Kedar

Barda

Rabinowitz

et al. 2022

Preprint

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Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express the β-glucan receptor Dectin-1, and respond to commensal fungi and β-glucans. In phagocytes, Dectin-1 mediates LC3 associated phagocytosis (LAP) utilizing autophagy components to process extracellular cargo. Dectin-1 can mediate phagocytosis of β-glucan-containing particles by non-phagocytic cells. We aimed to determine whether human IECs phagocytose β-glucan-containing fungal particles via LAP. Zymosan (β-glucan particle) and Heat-killed and UV inactivated C. albicans were phagocytosed by monolayers of human colonic (n=18) and ileal (n=4) organoids and IEC lines. LAP was identified by LC3 and Rubicon recruitment to phagosomes and lysosomal processing of internalized particles was demonstrated by co-localization with lysosomal dyes and LAMP2. Phagocytosis was significantly diminished by blockade of Dectin-1, actin polymerization and NAPDH oxidases. Our results show that human IECs sense luminal fungal particles and internalize them via LAP. This novel mechanism of luminal sampling suggests that IECs may contribute to the maintenance of mucosal tolerance towards commensal fungi.

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“…Lignin that contains mannose in the polysaccharide portion has been reported to stimulate the expression of the mRNA of dectin-2 [ 54 ], a C-type lectin receptor that recognizes high-mannose polysaccharides [ 55 ]. Research into the distribution of dectin-2 in oral tissues and its role in immunopotentiation is underway.…”

Section: Discussionmentioning

confidence: 99%

Lignosulfonate Rapidly Inactivates Human Immunodeficiency and Herpes Simplex Viruses

et al. 2021

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Very few studies of the antiviral potential of lignosulfonates have been published. With the aim of oral application, among various groups of natural products, the relative antiviral potency of lignosulfonate and its ability to rapidly inactivate viruses were investigated. Methods: As target cells, MT-4 cells in suspension and attached Vero cells were used for infections with human immunodeficiency virus (HIV) and human herpes simplex type-1 virus (HSV). Mock- or virus-infected cells were incubated for 3–5 days with various concentrations of test samples, and the viable cell number was determined with the MTT method. For the shorter exposure experiments, higher titers of HIV or HSV were exposed to test samples for 10 or 3 min, diluted to a normal multiplicity of infection (MOI), and applied to the cells. Antiviral activity was quantified by using the chemotherapy index. Results: In the long-exposure system, lignosulfonates showed comparable anti-HIV activity with those of AZT, ddC, and sulfated polysaccharides, and it exceeded those of hundreds of tannins and flavonoids. When the exposure time was shortened, the chemotherapeutic index of the lignosulfonates for HIV was increased 27-fold. At a physiological pH, lignosulfonate showed higher anti-HIV activity than commercial alkali-lignin, dealkali-lignin, and humic acid, possibly due to the higher solubility and purity. Conclusions: With their rapid virus-inactivation capabilities, lignosulfonates may be useful for the prevention or treatment of virally induced oral diseases.

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Role of Dectin-2 in the Phagocytosis of Cryptococcus neoformans by Dendritic Cells

Cited by 19 publications

References 38 publications

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic

Human intestinal epithelial cells can internalize luminal fungi via LC3-associated phagocytosis

Lignosulfonate Rapidly Inactivates Human Immunodeficiency and Herpes Simplex Viruses

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