Establishment of an &lt;em&gt;In vitro&lt;/em&gt; System to Study Intracellular Behavior of &lt;em&gt;Candida glabrata&lt;/em&gt; in Human THP-1 Macrophages

Nandan, Maruti; Borah, Sapan; Bairwa, Gaurav; Balusu, Sriram; Gorityala, Neelima; Kaur, Rupinder

doi:10.3791/50625

Cited by 8 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In other instances, smaller fungal bodies of 0.4–1 μm were evident depending on the field analysed. The 0.4–1 and the 1–2 μm-sized bodies are similar to those previously reported for some intracellular yeast cells 30 31 32 . These intracellular forms are known as endomycosomes 29 33 .…”

Section: Resultssupporting

confidence: 89%

Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

Pisa

Alonso

Rábano

et al. 2015

Sci Rep

208

181

View full text Add to dashboard Cite

The possibility that Alzheimer’s disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.

show abstract

Section: Resultssupporting

confidence: 89%

Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

Pisa

Alonso

Rábano

et al. 2015

Sci Rep

208

181

View full text Add to dashboard Cite

show abstract

“…In contrast, several neurons were immunopositive for C. glabrata and stained intracellular punctate bodies in the cytoplasm in ALS brain sections (Figure 3 ). These bodies resemble the intracellular morphology of other fungi, as reported previously 35 , 36 . This fungal material was not observed in all neurons, because some of them were devoid of it.…”

Section: Resultssupporting

confidence: 87%

Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with Amyotrophic Lateral Sclerosis

Alonso¹,

Pisa²,

Marina³

et al. 2015

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients.

show abstract

“…These observations are consistent with findings from other laboratories reporting intracellular infec-tion of mammalian cells by several fungi [22][23][24][25]. Initially, we wished to demonstrate that yeast can also be internalized in different tissues in mice.…”

Section: Immunohistochemical Analysis Of Tissues From Mice Infected Wsupporting

confidence: 90%

“…There is a paucity of studies on intracellular infection of non-phagocytic cells by fungi [21]. The majority of these studies have been carried out with monocyte cell lines and macrophages [22][23][24][25]. Future studies in this direction will benefit from the development of new antibodies and other reagents that will serve to examine the presence of fungal infections in neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…C. glabrata was employed for several reasons: this yeast gives rise to intracellular infection of culture cells [23] and also we have obtained rabbit antibodies against this yeast. Four nude mice were infected by intravenous injection of 5.8 × 10 6 colony forming units (cfu) of C. glabrata in 0.3 ml of phosphate-buffered saline (PBS).…”

Section: Mouse Infection With C Glabratamentioning

confidence: 99%

See 1 more Smart Citation

Direct Visualization of Fungal Infection in Brains from Patients with Alzheimer's Disease

Pisa

Alonso

Juarranz

et al. 2014

JAD

View full text Add to dashboard Cite

Recently, we have reported the presence of fungal infections in patients with Alzheimer's disease (AD). Accordingly, fungal proteins and DNA were found in brain samples, demonstrating the existence of infection in the central nervous system. In the present work, we raised antibodies to specific fungal species and performed immunohistochemistry to directly visualize fungal components inside neurons from AD patients. Mice infected with Candida glabrata were initially used to assess whether yeast can be internalized in mammalian tissues. Using polyclonal rabbit antibodies against C. glabrata, rounded immunopositive cells could be detected in the cytoplasm of cells from liver, spleen, and brain samples in infected, but not uninfected, mice. Immunohistochemical analyses of tissue from the frontal cortex of AD patients revealed the presence of fungal material in a small percentage (~10%) of cells, suggesting the presence of infection. Importantly, this immunopositive material was absent in control samples. Confocal microscopy indicated that this fungal material had an intracellular localization. The specific morphology of this material varied between patients; in some instances, disseminated material was localized to the cytoplasm, whereas small punctate bodies were detected in other patients. Interestingly, fungal material could be revealed using different anti-fungal antibodies, suggesting multiple infections. In summary, fungal infection can only be observed using specific anti-fungal antibodies and only a small percentage of cells contain fungi. Our findings provide an explanation for the hitherto elusive detection of fungi in AD brains, and are consistent with the idea that fungal cells are internalized inside neurons.

show abstract

Establishment of an <em>In vitro</em> System to Study Intracellular Behavior of <em>Candida glabrata</em> in Human THP-1 Macrophages

Cited by 8 publications

References 14 publications

Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with Amyotrophic Lateral Sclerosis

Direct Visualization of Fungal Infection in Brains from Patients with Alzheimer's Disease

Contact Info

Product

Resources

About