Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Buskirk AD[original query] |
---|
Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection
Oliva Chávez AS , Wang X , Marnin L , Archer NK , Hammond HL , Carroll EEM , Shaw DK , Tully BG , Buskirk AD , Ford SL , Butler LR , Shahi P , Morozova K , Clement CC , Lawres L , Neal AJO , Mamoun CB , Mason KL , Hobbs BE , Scoles GA , Barry EM , Sonenshine DE , Pal U , Valenzuela JG , Sztein MB , Pasetti MF , Levin ML , Kotsyfakis M , Jay SM , Huntley JF , Miller LS , Santambrogio L , Pedra JHF . Nat Commun 2021 12 (1) 3696 Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases. |
A murine inhalation model to characterize pulmonary exposure to dry Aspergillus fumigatus conidia
Buskirk AD , Green BJ , Lemons AR , Nayak AP , Goldsmith WT , Kashon ML , Anderson SE , Hettick JM , Templeton SP , Germolec DR , Beezhold DH . PLoS One 2014 9 (10) e109855 Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (Deltaalb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1x105 twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Deltaalb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants. |
Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures
Buskirk AD , Templeton SP , Nayak AP , Hettick JM , Law BF , Green BJ , Beezhold DH . J Immunotoxicol 2013 11 (2) 180-9 Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Deltaarp2 (tan) or Deltaalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Deltaalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8+ IL-17+ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia. |
Role of germination in murine airway CD8 T-cell responses to Aspergillus conidia
Templeton SP , Buskirk AD , Law B , Green BJ , Beezhold DH . PLoS One 2011 6 (4) e18777 Pulmonary exposure to Aspergillus fumigatus has been associated with morbidity and mortality, particularly in immunocompromised individuals. A. fumigatus conidia produce beta-glucan, proteases, and other immunostimulatory factors upon germination. Murine models have shown that the ability of A. fumigatus to germinate at physiological temperature may be an important factor that facilitates invasive disease. We observed a significant increase in IFN-gamma-producing CD8(+) T cells in bronchoalveolar lavage fluid (BALF) of immunocompetent mice that repeatedly aspirated A. fumigatus conidia in contrast to mice challenged with A. versicolor, a species that is not typically associated with invasive, disseminated disease. Analysis of tissue sections indicated the presence of germinating spores in the lungs of mice challenged with A. fumigatus, but not A. versicolor. Airway IFN-gamma(+)CD8(+) T-cells were decreased and lung germination was eliminated in mice that aspirated A. fumigatus conidia that were formaldehyde-fixed or heat-inactivated. Furthermore, A. fumigatus particles exhibited greater persistence in the lungs of recipient mice when compared to non-viable A. fumigatus or A. versicolor, and this correlated with increased maintenance of airway memory-phenotype CD8(+) T cells. Therefore, murine airway CD8(+) T cell-responses to aspiration of Aspergillus conidia may be mediated in part by the ability of conidia to germinate in the host lung tissue. These results provide further evidence of induction of immune responses to fungi based on their ability to invade host tissue. |
Fungal pigments inhibit the MALDI-TOF mass spectrometry analysis of darkly pigmented fungi
Buskirk AD , Hettick JM , Chipinda I , Law BF , Siegel PD , Slaven JE , Green BJ , Beezhold DH . Anal Biochem 2010 411 (1) 122-8 Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used to discriminate monilaceous fungal species, however, darkly pigmented fungi yield poor fingerprint mass spectra that contain few peaks of low relative abundance. In this study, the effect of dark fungal pigments on the observed MALDI mass spectra was investigated. Peptide and protein samples containing varying concentrations of synthetic melanin or fungal pigments extracted from Aspergillus niger were analyzed by MALDI-TOF and MALDI-qTOF MS. Signal suppression was observed in samples containing greater than 25 ng/muL pigment. Microscopic examination of the MALDI sample deposit was usually heterogeneous, with regions of high pigment concentration appearing black. Acquisition of MALDI mass spectra from these darkly pigmented regions of the sample deposit yielded poor or no [M+H](+) ion signal. In contrast, non-pigmented regions within the sample deposit and hyphal negative control extracts of A. niger were not inhibited. This study demonstrated that dark fungal pigments inhibited the desorption/ionization process during MALDI-MS; however these fungi may be successfully analyzed by MALDI-TOF MS when culture methods that suppress pigment expression are used. Addition of tricyclazole to the fungal growth media blocks fungal melanin synthesis and results in less-melanized fungi that may be analyzed by MALDI-TOF MS. |
Murine models of airway fungal exposure and allergic sensitization
Templeton SP , Buskirk AD , Green BJ , Beezhold DH , Schmechel D . Med Mycol 2010 48 (2) 217-28 Inhalation of common indoor filamentous fungi has been associated with the induction or exacerbation of allergic respiratory disease. The understanding of fungal inhalation and allergic sensitization has significantly advanced with the use of small animal models, especially mouse models. Numerous studies have employed different animal exposure and sensitization techniques, each with inherent advantages and disadvantages that are addressed in this review. In addition, most studies involve exposure of animals to fungal spores or spore extracts while neglecting the influence of hyphal or subcellular fragment exposures. Recent literature examining the potential for hyphae and fungal fragments to induce or exacerbate allergy is discussed. Innate immune recognition of fungal elements and their contribution to lung allergic inflammation in animal models are also reviewed. Though physical properties of fungi play an important role following exposure, host immune development is also critical in airway inflammation and allergy. We discuss the importance of environmental factors that influence early immune development and subsequent susceptibility to allergy. Murine studies that examine the role of intestinal microflora and prenatal or early life environmental factors that promote allergic sensitization are also evaluated. Future studies will require animal models that accurately reflect natural fungal exposures and identify environmental factors that influence immune development and thus promote respiratory fungal allergy and disease. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 06, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure