Abstract:
:Candida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall beta-glucan from immune recognition, mutes protective host responses mediated by the Dectin-1 beta-glucan receptor on innate immune cells. Although the ability of C. albicans to switch between a yeast- or hyphal-form is a key virulence determinant, the role of each morphotype in beta-glucan masking during infection and treatment has not been addressed. Here, we show that during infection of mice, the C. albicans beta-glucan is masked initially but becomes exposed later in several organs. At all measured stages of infection, there is no difference in beta-glucan exposure between yeast-form and hyphal cells. We have previously shown that sub-inhibitory doses of the anti-fungal drug caspofungin can expose beta-glucan in vitro, suggesting that the drug may enhance immune activity during therapy. This report shows that caspofungin also mediates beta-glucan unmasking in vivo. Surprisingly, caspofungin preferentially unmasks filamentous cells, as opposed to yeast form cells, both in vivo and in vitro. The fungicidal activity of caspofungin in vitro is also filament-biased, as corroborated using yeast-locked and hyphal-locked mutants. The uncloaking of filaments is not a general effect of anti-fungal drugs, as another anti-fungal agent does not have this effect. These results highlight the advantage of studying host-pathogen interaction in vivo and suggest new avenues for drug development.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Wheeler RT,Kombe D,Agarwala SD,Fink GRdoi
10.1371/journal.ppat.1000227subject
Has Abstractpub_date
2008-12-01 00:00:00pages
e1000227issue
12eissn
1553-7366issn
1553-7374journal_volume
4pub_type
杂志文章相关文献
PLoS Pathogens文献大全abstract::The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell-mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000392
更新日期:2009-04-01 00:00:00
abstract::Host heterogeneity in disease transmission is widespread but precisely how different host traits drive this heterogeneity remains poorly understood. Part of the difficulty in linking individual variation to population-scale outcomes is that individual hosts can differ on multiple behavioral, physiological and immunolo...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1009196
更新日期:2021-01-19 00:00:00
abstract::Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-ad...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008180
更新日期:2019-12-16 00:00:00
abstract::Cells of the immune system are derived from hematopoietic stem cells (HSCs) residing in the bone marrow. HSCs become activated in response to stress, such as acute infections, which adapt the bone marrow output to the needs of the immune response. However, the impact of infection-adapted HSC activation and differentia...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006422
更新日期:2017-08-07 00:00:00
abstract::Pomalidomide (Pom) is an immunomodulatory drug that has efficacy against Kaposi's sarcoma, a tumor caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Pom also induces direct cytotoxicity in primary effusion lymphoma (PEL), a B-cell malignancy caused by KSHV, in part through downregulation of IRF4, cMyc, and CK1...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1009091
更新日期:2021-01-07 00:00:00
abstract::Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II) deposits as amyloid fibrils (AApoAII) and can be transmitted from one animal to another bo...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000914
更新日期:2010-05-20 00:00:00
abstract::Paramount to the success of persistent viral infection is the ability of viruses to navigate hostile environments en route to future targets. In response to such obstacles, many viruses have developed the ability of establishing actin rich-membrane bridges to aid in future infections. Herein through dynamic imaging of...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002762
更新日期:2012-01-01 00:00:00
abstract::Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine) immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may als...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003615
更新日期:2013-09-01 00:00:00
abstract::Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural p...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005998
更新日期:2016-11-01 00:00:00
abstract::Type III secretion systems (T3SS) are nano-syringes used by a wide range of Gram-negative pathogens to promote infection by directly injecting effector proteins into targeted host cells. Translocation of effectors is triggered by host-cell contact and requires assembly of a pore in the host-cell plasma membrane, which...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005530
更新日期:2016-03-29 00:00:00
abstract::The human T cell leukemia virus HTLV-1 establishes a persistent infection in vivo in which the viral sense-strand transcription is usually silent at a given time in each cell. However, cellular stress responses trigger the reactivation of HTLV-1, enabling the virus to transmit to a new host cell. Using single-molecule...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008164
更新日期:2019-11-18 00:00:00
abstract::The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses orig...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000590
更新日期:2009-09-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is a global public health burden for which no licensed vaccine exists. To aid vaccine development via increased understanding of the protective antibody response to RSV prefusion glycoprotein F (PreF), we performed structural and functional studies using the human neutralizing antibod...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008943
更新日期:2020-11-02 00:00:00
abstract::Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far abou...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1006705
更新日期:2017-10-27 00:00:00
abstract::More than half of the world population is at risk of dengue virus (DENV) infection because of the global distribution of its mosquito vectors. DENV is an envelope virus that relies on host lipid membranes for its life-cycle. Here, we characterized how DENV hijacks the mosquito lipidome to identify targets for novel tr...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008199
更新日期:2019-12-09 00:00:00
abstract::In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenit...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1005755
更新日期:2016-07-07 00:00:00
abstract::Antigenic variation to evade host immunity has long been assumed to be a driving force of diversifying selection in pathogens. Colonization by Streptococcus pneumoniae, which is central to the organism's transmission and therefore evolution, is limited by two arms of the immune system: antibody- and T cell- mediated i...
journal_title:PLoS pathogens
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1371/journal.ppat.1002989
更新日期:2012-01-01 00:00:00
abstract::Type I interferons (T1-IFN) are critical in the innate immune response, acting upon infected and uninfected cells to initiate an antiviral state by expressing genes that inhibit multiple stages of the lifecycle of many viruses. T1-IFN triggers the production of Interferon-Stimulated Genes (ISGs), activating an antivir...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007778
更新日期:2019-10-11 00:00:00
abstract::The 14-3-3 molecular scaffolds promote type I interferon (IFN) responses by stabilizing the interaction of RIG-I with the TRIM25 ligase. Viruses have evolved unique strategies to halt this cellular response to support their replication and spread. Here, we report that the ubiquitin deconjugase (DUB) encoded in the N-t...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008146
更新日期:2019-11-11 00:00:00
abstract::The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of the caecum and proximal colon of their hosts causing the human disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the inflammatory response elicited by the parasite while tunnelling through intes...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007265
更新日期:2019-01-14 00:00:00
abstract::Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1004811
更新日期:2015-04-14 00:00:00
abstract::Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000373
更新日期:2009-04-01 00:00:00
abstract::Hepatitis C virus (HCV) nonstructural protein 2 (NS2) is a hydrophobic, transmembrane protein that is required not only for NS2-NS3 cleavage, but also for infectious virus production. To identify cellular factors that interact with NS2 and are important for HCV propagation, we screened a human liver cDNA library by sp...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1003589
更新日期:2013-01-01 00:00:00
abstract::The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling ...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1000192
更新日期:2008-10-01 00:00:00
abstract::Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggre...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002522
更新日期:2012-02-01 00:00:00
abstract::HIV and other lentiviruses can productively infect nondividing cells, whereas most other retroviruses, such as murine leukemia virus, require cell division for efficient infection. However, the determinants for this phenotype have been controversial. Here, we show that HIV-1 capsid (CA) is involved in facilitating HIV...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.0030156
更新日期:2007-10-26 00:00:00
abstract::It has been proposed that in wild ecosystems viruses are often plant mutualists, whereas agroecosystems favour pathogenicity. We seek evidence for virus pathogenicity in wild ecosystems through the analysis of plant-virus coevolution, which requires a negative effect of infection on the host fitness. We focus on the i...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1007810
更新日期:2019-05-28 00:00:00
abstract::Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in differen...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002080
更新日期:2011-06-01 00:00:00
abstract::Promyelocytic leukemia protein (PML) has antiviral functions and many viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infe...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1002157
更新日期:2011-08-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) infection is a chronic condition, where viral DNA integrates into the genome. Latently infected cells form a persistent, heterogeneous reservoir that at any time can reactivate the integrated HIV-1. Here we confirmed that latently infected cells from HIV-1 positive study par...
journal_title:PLoS pathogens
pub_type: 杂志文章
doi:10.1371/journal.ppat.1008264
更新日期:2020-01-30 00:00:00