Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Lee, Pamela; Lau, Yu Lung

doi:10.3389/fimmu.2017.00735

Cited by 67 publications

(59 citation statements)

References 178 publications

(270 reference statements)

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“…that tested positive for Cryptoccoccus spp. was also positive for P. brasiliensis, resulting in a coinfection and this sample is a rodent road-killed in Florestal Gateados, this reinforce with the literature that P. brasiliensis is found in tropical regions 48 and Cryptococcus spp. in species of Eucaliptus.…”

Section: Roads and Highways Are Examples Of Anthropic Interventions Wsupporting

confidence: 88%

Molecular detection of fungi of public health importance in wild animals from Southern Brazil

Losnak

Rocha

Almeida

et al. 2018

Mycoses

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Some animals have an important relationship with fungal infections, and searching for pathogens in animal samples may be an opportunity for eco-epidemiological research. Since studies involving wildlife are generally restricted, using samples from road kills is an alternative. The aim of this study was to verify whether pathogenic fungi of public health importance occur in wildlife road kills from Santa Catarina State, Brazil. Organ samples (n = 1063) from 297 animals were analysed according to Polymerase Chain Reaction (PCR) using universal primers to detect fungi in general and, subsequently, using primers specific to Paracoccidioides brasiliensis, Histoplasma capsulatum and Cryptococcus spp. There were 102 samples positive for fungal species. Eight samples were positive for P. brasiliensis, three samples were positive for Cryptococcus spp. and one sample had coinfection by these two fungi. No sample was positive for Histoplasma spp. according to the molecular detection. Genetic sequencing allowed the identification of Fungal sp. in 89 samples, Cryptococcus neoformans in two samples and Aspergillus penicillioides in three samples. This study shows the importance of wild animals in the epidemiology of fungal infections and assists in the mapping of pathogen occurrence in a region that was not previously evaluated.

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Section: Roads and Highways Are Examples Of Anthropic Interventions Wsupporting

confidence: 88%

Molecular detection of fungi of public health importance in wild animals from Southern Brazil

Losnak

Rocha

Almeida

et al. 2018

Mycoses

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“…Unlike the high incidence of hepatic complications often associated with infection by Cryptosporidium species reported in Europe and Japan, no one in our cohort exhibited sclerosing cholangitis or liver cirrhosis. Recently, Pamela P. Lee discussed endemic mycoses in PIDs, in which she highlighted the Talaromyces marneffei infection in CD40L deficiency in South‐East Asia . In our cohort, six patients (15%) were diagnosed with T. marneffei infection by blood or bone morrow culture; all presented initially with prolonged fever and cough, along with other non‐specific symptoms such as a sore throat, neck pain, lymphadenopathy or hepatosplenomegaly.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, Pamela P. Lee discussed endemic mycoses in PIDs, in which she highlighted the Talaromyces marneffei infection in CD40L deficiency in South-East Asia. 26 In our cohort, six patients (15%) were diagnosed with T. marneffei infection by blood or bone morrow culture; all presented initially with prolonged fever and cough, along with other non-specific symptoms such as a sore throat, neck pain, lymphadenopathy or hepatosplenomegaly. Thus, the results suggest that Talaromyces marneffei is one of the main opportunistic pathogens in patients with CD40L deficiency in China and South-East Asia.…”

Section: Discussionmentioning

confidence: 89%

Clinical, genetic and immunological characteristics of 40 Chinese patients with CD40 ligand deficiency

Tang

Chen

et al. 2019

Scand J Immunol

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CD40 ligand (CD40L) deficiency is a rare but life‐threatening primary immunodeficiency caused by mutations in the CD40L gene. Here, we investigated a cohort of 40 genetically diagnosed CD40L‐deficient patients from the Chinese mainland, analysed their clinical and genetic data, and examined CD40L expression, the proportion of T cell subsets, B cell subsets and T follicular helper (Tfh) cells. The aim was to provide a complete picture of CD40L deficiency. Initial presentations of the patient cohort mainly involved recurrent fever (47.5%) and sinopulmonary infection (42.5%). Life‐threatening infections (42.5%), caused by various pathogens, were the most serious threats faced by CD40L‐deficient patients, while neutropenia (57.5%) remained the most common complication. Opportunistic infections, including Pneumocystis carinii pneumonia and invasive fungal disease associated with Talaromyces marneffei, were also common in the cohort. In addition, seven patients (17.5%) suffered BCGitis/BCGosis, which is a major problem facing a planned immunization programme in China. It was intriguing that reduced IgM levels were observed in 12.5% of patients, while normal or elevated IgA levels were shown in 47.5% of patients. Thirty‐seven unique mutations were identified in 40 patients; of these, 10 were novel. Furthermore, we observed a lower percentage of NK cells, Tfh cells, and central memory CD4+ T cells, and an extremely small class‐switched memory B cell population, in CD40L‐deficient patients. Patients who underwent hematopoietic stem cell transplantation experienced better disease remission. Taken together, our data establish the largest database about CD40L deficiency in China and provide genetic, immunologic and clinical information about Chinese CD40L‐deficient patients.

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“…The discovery of PIDs underlying invasive fungal diseases (IFDs), in patients with or without other infectious diseases, has helped to identify critical pathways in immunity to some IFDs [36]. For example, chronic granulomatous disease (CGD), caused by inherited defects affecting the function of the phagocyte NADPH oxidase complex, is characterized by recurrent life-threatening bacterial and fungal diseases, mostly caused by Aspergillus spp.…”

Section: Invasive Fungal Diseases: Inborn Errors Of Card9 Immunitymentioning

confidence: 99%

Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals

Vinh

Casanova³

et al. 2017

Current Opinion in Microbiology

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It has been estimated that there are at least 1.5 million fungal species, mostly present in the environment, but only a few of these fungi cause human disease. Most fungal diseases are self-healing and benign, but some are chronic or life-threatening. Acquired and inherited defects of immunity, including breaches of mucocutaneous barriers and circulating leukocyte deficiencies, account for most severe modern-day mycoses. Other types of infection typically accompany these fungal infections. More rarely, severe fungal diseases can strike otherwise healthy individuals. Historical reports of fungi causing chronic peripheral (e.g. affecting the nails, skin, hair) infections, and invasive disease (e.g. brain, lungs, liver), in otherwise healthy patients, can be traced back to the mid-20th century. These fungi typically cause endemic, but not epidemic diseases, are more likely to underlie sporadic than familial cases, and only threaten a small proportion of infected individuals. The basis of this “idiosyncratic” susceptibility has long remained unexplained, but it has recently become apparent that “idiopathic” fungal diseases, in children, teenagers, and even adults, may be caused by single-gene inborn errors of immunity. The study of these unusual primary immunodeficiencies (PIDs) has led to the identification of molecules and cells playing a crucial role in human host defenses against certain fungi at particular anatomic sites. A picture is emerging of inborn errors of IL-17 immunity selectively underlying chronic mucocutaneous candidiasis, with little inter-individual variability, and of inborn errors of CARD9 immunity underlying various life-threatening invasive fungal diseases, differing between patients.

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Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

Cited by 67 publications

References 178 publications

Molecular detection of fungi of public health importance in wild animals from Southern Brazil

Molecular detection of fungi of public health importance in wild animals from Southern Brazil

Clinical, genetic and immunological characteristics of 40 Chinese patients with CD40 ligand deficiency

Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals

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