Lysosomes and the "toxicity" of Rickettsials. II. Non-cytocidal interactions of egg-grown C. psittaci 6BC and in vitro macrophages

1972 ◽  
Vol 18 (6) ◽  
pp. 869-873 ◽  
Author(s):  
Nonna Kordová ◽  
Linda Poffenroth ◽  
John C. Wilt
Keyword(s):  
Acid Phosphatase ◽  
Cell Damage ◽  
Giant Cells ◽  
Host Cells ◽  
Marked Contrast ◽  
Lysosomal Acid ◽  
Cytoplasmic Vacuoles ◽  
L Cell

During the infection of cultured mouse peritoneal phagocytes with egg-grown C. psittaci 6BC strain, lysosomes retained their integrity and host cells were not damaged. Infected monocytes showed greater ability than uninfected monocytes to spread and transform into giant cells containing enlarged nuclei and masses of cytoplasm with clear cytoplasmic vacuoles. Chlamydial particles were released from the cytoplasm of infected phagocytes by pseudopodia-like extrusions. These events were in marked contrast to the effect of L cell grown C. psittaci 6BC strain which caused early leakage of lysosomal acid phosphatase into the cytoplasm of macrophages and induced a rapidly progressive irreversible cell damage (14).

Lysosomes and the "toxicity" of Rickettsials. III. Response of L cells infected with egg-attenuated C. psittaci 6BC strain

1972 ◽  
Vol 18 (8) ◽  
pp. 1343-1348 ◽  
Author(s):  
Nonna Kordová ◽  
Linda Poffenroth ◽  
John C. Wilt
Keyword(s):  
Cell Culture ◽  
Acid Phosphatase ◽  
Comparative Studies ◽  
Post Infection ◽  
Marked Contrast ◽  
Lysosomal Acid ◽  
L Cells ◽  
L Cell ◽  
Infected Cells

During the infection of L cells (clone 60 and 929) with egg-grown C. psittaci 6BC strain, lyosomes retained their integrity and L cells were not injured. Infected cells proliferated more intensely and showed higher mitotic indices from 24 h post infection than noninfected control cells. Chlamydial inclusions were released from the cytoplasm of infected L cells by pseudopodia-like extrusions. These events were in marked contrast to the effect of the L cell grown C. psittaci 6BC strain which caused activation of lysosomal acid phosphatase and damage of L cells. Previous comparative studies of the host lysosomal response to egg-grown as compared to cell culture grown C. psittaci 6BC strain in cultured macrophages and L cells are discussed.

scholarly journals Coxiella burnetiiAcid Phosphatase Inhibits the Release of Reactive Oxygen Intermediates in Polymorphonuclear Leukocytes

2010 ◽  
Vol 79 (1) ◽  
pp. 414-420 ◽  
Author(s):  
J. Hill ◽  
J. E. Samuel
Keyword(s):  
Acid Phosphatase ◽  
Nadph Oxidase ◽  
Polymorphonuclear Leukocytes ◽  
Q Fever ◽  
Reactive Oxygen ◽  
Host Cells ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates

ABSTRACTCoxiella burnetii, the etiological agent of Q fever, is a small, Gram-negative, obligate intracellular bacterium. Replication ofC. burnetiiduring infection has been shown to be increased by decreasing oxidative stress using p47phox −/−and iNOS−/−micein vivoand by pharmacologic inhibitorsin vitro. Building upon this model, we investigated the role polymorphonuclear leukocytes (PMN) play in the control of infection, since NADPH oxidase-mediated release of reactive oxygen intermediates (ROI) is a primary bactericidal mechanism for these cells that is critical for early innate clearance. Earlier studies suggested thatC. burnetiiactively inhibited release of ROI from PMN through expression of an unidentified acid phosphatase (ACP). Recent genomic annotations identified one open reading frame (CBU0335) which may encode a Sec- and type II-dependent secreted ACP. To test this model, viableC. burnetiipropagated in tissue culture host cells or axenic media,C. burnetiiextracts, or purified recombinant ACP (rACP) was combined with human PMN induced with 4-phorbol 12-myristate 13-acetate (PMA). The release of ROI was inhibited when PMN were challenged with viableC. burnetii,C. burnetiiextracts, or rACP but not when PMN were challenged with electron beam-inactivatedC. burnetii. C. burnetiiextracts and rACP were also able to inhibit PMA-induced formation of NADPH oxidase complex on PMN membranes, suggesting a molecular mechanism responsible for this inhibition. These data support a model in whichC. burnetiieludes the primary ROI killing mechanism of activated PMN by secreting at least one acid phosphatase.

Lysosomes and the "toxicity" of Rickettsiales. IV. Ultrastructural studies of macrophages infected with a cytopathic L cell-grown C. psittaci 6BC strain

1973 ◽  
Vol 19 (3) ◽  
pp. 315-320 ◽  
Author(s):  
Nonna Kordová ◽  
Jan Hoogstraten ◽  
John C. Wilt
Keyword(s):  
Acid Phosphatase ◽  
Neutral Red ◽  
Contributory Factor ◽  
Enzyme Release ◽  
High Concentration ◽  
Ultrastructural Studies ◽  
Cytoplasmic Organelles ◽  
L Cell ◽  
Mouse Macrophages

Mouse macrophages in vitro inoculated with a low dose of a cytopathic L cell-grown C. psittaci 6BC strain were harvested at times when a delayed cytopathic effect (CPE) was observed by light microscopy and when a cytochemical test for acid phosphatase revealed lysosomal enzyme release. An array of different lysosomal types was revealed by ultrastructural studies such as digestive vesicles with single or double outer membranes and whorls of membranes, dense residual bodies, aggregated and single scattered ferritin-like granules, and fragments of membranes. Enlargement of cysternae of endoplasmic reticulum, disintegration of cytoplasmic organelles, and thinning of ground cytoplasm were also observed. Cytoplasmic degeneration has been observed both within membrane-limited structures and in wider areas not limited by recognizable membranes.A high concentration of the agent resulted in an early toxic effect; this was accompanied by a rapid vacuolization of the cytoplasm of the macrophages which showed a poorly developed ultrastructure, and absence of mitochondria and cytoplasmic organelles. Cytochemical tests indicated that these alterations correlated with release of lysosomal acid phosphatase and disintegration of neutral red stained granules. Ultrastructural studies support the view that disintegration of lysosomes may be considered an important contributory factor in the pathology of chlamydial infection.

scholarly journals Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2994
Author(s):  
Xiaodan Jiao ◽  
Maryam Rahimi Balaei ◽  
Ejlal Abu-El-Rub ◽  
Filippo Casoni ◽  
Hassan Pezeshgi Modarres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acid Phosphatase ◽  
Granule Cell ◽  
Granule Cells ◽  
Mutant Mice ◽  
Lysosomal Acid ◽  
Protein Synthesis Machinery

Lysosomal acid phosphatase 2 (Acp2) mutant mice (naked-ataxia, nax) have a severe cerebellar cortex defect with a striking reduction in the number of granule cells. Using a combination of in vivo and in vitro immunohistochemistry, Western blotting, BrdU assays, and RT-qPCR, we show downregulation of MYCN and dysregulation of the SHH signaling pathway in the nax cerebellum. MYCN protein expression is significantly reduced at P10, but not at the peak of proliferation at around P6 when the number of granule cells is strikingly reduced in the nax cerebellum. Despite the significant role of the SHH–MycN pathway in granule cell proliferation, our study suggests that a broader molecular pathway and additional mechanisms regulating granule cell development during the clonal expansion period are impaired in the nax cerebellum. In particular, our results indicate that downregulation of the protein synthesis machinery may contribute to the reduced number of granule cells in the nax cerebellum.

scholarly journals Phagosome-lysosome fusion inhibited by algal symbionts of Hydra viridis.

1982 ◽  
Vol 94 (1) ◽  
pp. 56-63 ◽  
Author(s):  
T C Hohman ◽  
P L McNeil ◽  
L Muscatine
Keyword(s):  
Acid Phosphatase ◽  
Host Cells ◽  
Digestive Cells ◽  
Symbiotic Algae ◽  
Algal Symbionts ◽  
Dimethyl Urea ◽  
Photosynthetic Products ◽  
Basal Position ◽  
Hydra Viridis

Certain species of Chlorella live within the digestive cells of the fresh water cnidarian Hydra viridis. When introduced into the hydra gut, these symbiotic algae are phagocytized by digestive cells but avoid host digestion and persist at relatively constant numbers within host cells. In contrast, heat-killed symbionts are rapidly degraded after phagocytosis. Live symbionts appear to persist because host lysosomes fail to fuse with phagosomes containing live symbionts. Neither acid phosphatase nor ferritin was delivered via lysosomes into phagosomes containing live symbionts, whereas these lysosomal markers were found in 50% of the vacuoles containing heat-killed symbionts 1 h after phagocytosis. Treatment of symbiotic algae before phagocytosis with polycationic polypeptides abolishes algal persistence and perturbs the ability of these algae to control the release of photosynthate in vitro. Similarly, inhibition of photosynthesis and hence of the release of photosynthetic products as a result of prolonged darkness and 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU) treatment also abolishes persistence. Symbiotic algae are not only protected from host digestive attack but are also selectively transported within host cells, moving from the apical site of phagocytosis to a basal position of permanent residence. This process too is disrupted by polycationic polypeptides, DCMU and darkness. Both algal persistence and transport may, therefore, be a function of the release of products from living, photosynthesizing symbionts. Vinblastine treatment of host animals blocked the movement of algae within host cells but did not perturb algal persistence: algal persistence and the transport of algae may be initiated by the same signal, but they are not interdependent processes.

scholarly journals Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of Escherichia coli O157:H7 during Host-Bacterial Interactions in vitro

Toxins ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 48 ◽  
Author(s):  
Bruballa ◽  
Shiromizu ◽  
Bernal ◽  
Pineda ◽  
Sabbione ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Time Course ◽  
Cell Damage ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Bacterial Survival ◽  
E Coli ◽  
Clinical Conditions

Enterohemorrhagic Escherichia coli (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing E. coli O157:H7 is the serotype most frequently associated with severe human disease. In this work we analyzed the hypothesis that host cells participate in Stx2 production, cell damage, and inflammation during EHEC infection. With this aim, macrophage-differentiated THP-1 cells and the intestinal epithelial cell line HCT-8 were incubated with E. coli O157:H7. A time course analysis of cellular and bacterial survival, Stx2 production, stx2 transcription, and cytokine secretion were analyzed in both human cell lines. We demonstrated that macrophages are able to internalize and kill EHEC. Simultaneously, Stx2 produced by internalized bacteria played a major role in macrophage death. In contrast, HCT-8 cells were completely resistant to EHEC infection. Besides, macrophages and HCT-8 infected cells produce IL-1β and IL-8 inflammatory cytokines, respectively. At the same time, bacterial stx2-specific transcripts were detected only in macrophages after EHEC infection. The interplay between bacteria and host cells led to Stx production, triggering of inflammatory response and cell damage, all of which could contribute to a severe outcome after EHEC infections.

scholarly journals Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

2009 ◽  
Vol 8 (10) ◽  
pp. 1498-1510 ◽  
Author(s):  
Hyunsook Park ◽  
Yaoping Liu ◽  
Norma Solis ◽  
Joshua Spotkov ◽  
Jessica Hamaker ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Candida Albicans ◽  
Epithelial Cells ◽  
Multiple Stressors ◽  
Cell Damage ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Transcriptional Responses ◽  
Oral Epithelial

ABSTRACT Candida albicans interacts with oral epithelial cells during oropharyngeal candidiasis and with vascular endothelial cells when it disseminates hematogenously. We set out to identify C. albicans genes that govern interactions with these host cells in vitro. The transcriptional response of C. albicans to the FaDu oral epithelial cell line and primary endothelial cells was determined by microarray analysis. Contact with epithelial cells caused a decrease in transcript levels of genes related to protein synthesis and adhesion, whereas contact with endothelial cells did not significantly influence any specific functional category of genes. Many genes whose transcripts were increased in response to either host cell had not been previously characterized. We constructed mutants with homozygous insertions in 22 of these uncharacterized genes to investigate their function during host-pathogen interaction. By this approach, we found that YCK2, VPS51, and UEC1 are required for C. albicans to cause normal damage to epithelial cells and resist antimicrobial peptides. YCK2 is also necessary for maintenance of cell polarity. VPS51 is necessary for normal vacuole formation, resistance to multiple stressors, and induction of maximal endothelial cell damage. UEC1 encodes a unique protein that is required for resistance to cell membrane stress. Therefore, some C. albicans genes whose transcripts are increased upon contact with epithelial or endothelial cells are required for the organism to damage these cells and withstand the stresses that it likely encounters during growth in the oropharynx and bloodstream.

scholarly journals LYSOSOMAL ACID HYDROLASES IN MICE INFECTED WITH BCG

1965 ◽  
Vol 121 (5) ◽  
pp. 727-738 ◽  
Author(s):  
Kazuhisa Saito ◽  
Emanuel Suter
Keyword(s):  
Acid Phosphatase ◽  
Liver Homogenate ◽  
Subcellular Fractions ◽  
The Other ◽  
Acid Phosphatases ◽  
Acid Hydrolases ◽  
Lysosomal Acid

Experiments are reported dealing with the increase of lysosomal acid hydrolases induced by BCG infection. Acid hydrolases were determined quantitatively in peritoneal MP, liver homogenate, and plasma of normal and BCG-infected mice. A significant increase of acid phosphatase, ß-glucuronidase, and cathepsin was found in MP and liver homogenate of BCG-infected mice. In plasma also a significant increase of acid phosphatase and ß-glucuronidase was noticed. The results of the determination of the enzymes in centrifugally separated subcellular fractions of liver homogenate indicated clearly that the acid hydrolases associated mainly with the "large granular" fraction, which consists of mitochondria, lysosomes, and microsomes and that infection with BCG caused significant increase of the enzymes specifically in this fraction. Differences in the pattern of location among centrifugally separated fraction of liver homogenate were observed between acid phosphatase and the other two acid hydrolases. MP cultured in vitro doubled their acid phosphatases content within 24 hours, whereas ß-glucuronidase rather decreased in the same cells.

scholarly journals Counteraction of HCV-Induced Oxidative Stress Concurs to Establish Chronic Infection in Liver Cell Cultures

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Simona Anticoli ◽  
Donatella Amatore ◽  
Paola Matarrese ◽  
Marta De Angelis ◽  
Anna Teresa Palamara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Viral Replication ◽  
Apoptotic Cell ◽  
Cell Damage ◽  
Infectious Clone ◽  
Chronic Phase ◽  
Hcv Infection ◽  
Host Cells

Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an in vitro system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection.

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