scholarly journals CXCR2 Blockade Influences Anaplasma phagocytophilum Propagation but Not Histopathology in the Mouse Model of Human Granulocytic Anaplasmosis

2004 ◽  
Vol 11 (5) ◽  
pp. 963-968 ◽  
Author(s):  
Diana G. Scorpio ◽  
Mustafa Akkoyunlu ◽  
Erol Fikrig ◽  
J. Stephen Dumler
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Tissue Injury ◽  
Treated Group ◽  
Obligate Intracellular Bacterium ◽  
Human Granulocytic Anaplasmosis ◽  
Obligate Intracellular ◽  
Liver Histopathology ◽  
Granulocytic Anaplasmosis ◽  
Infected Cells ◽  
And Control

ABSTRACT Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils and causes human granulocytic anaplasmosis. Infection induces neutrophil secretion of interleukin-8 or murine homologs and perpetuates infection by recruiting susceptible neutrophils. We hypothesized that antibody blockade of CXCR2 would decrease A. phagocytophilum tissue load by interrupting neutrophil recruitment but would not influence murine hepatic pathology. C3H-scid mice were treated with CXCR2 antiserum or control prior to or on day 14 after infection. Quantitative PCR and immunohistochemistry for A. phagocytophilum were performed and severity of liver histopathology was ranked. Control mice had more infected cells in tissues than the anti-CXCR2-treated group. The histopathological rank was not different between treated and control animals. Infected cells of control mice clustered in tissue more than in treated mice. The results support the hypothesis of bacterial propagation through chemokine induction and confirm that tissue injury is unrelated to A. phagocytophilum tissue load.

scholarly journals Anaplasma phagocytophilum Infection Induces Protracted Neutrophil Degranulation

2004 ◽  
Vol 72 (6) ◽  
pp. 3680-3683 ◽  
Author(s):  
Kyoung-seong Choi ◽  
Dennis J. Grab ◽  
J. Stephen Dumler
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Tissue Injury ◽  
Clinical Manifestations ◽  
Human Granulocytic Anaplasmosis ◽  
Granulocytic Anaplasmosis ◽  
Neutrophil Degranulation ◽  
Do So ◽  
Inflammatory Tissue

ABSTRACT Anaplasma phagocytophilum-infected neutrophil degranulation could exacerbate inflammation. Thus, the degranulation of infected neutrophils was assayed. Infected neutrophils expressed CD11b and CD66b, and supernatants of infected neutrophils showed more proMMP-9 and MMP-9 activity than controls and continued to do so for ≥18 h. Degranulation-related inflammatory tissue injury may account for some clinical manifestations in human granulocytic anaplasmosis.

scholarly journals Sequential Analysis of Anaplasma phagocytophilum msp2 Transcription in Murine and Equine Models of Human Granulocytic Anaplasmosis

2007 ◽  
Vol 15 (3) ◽  
pp. 418-424 ◽  
Author(s):  
Diana G. Scorpio ◽  
Christian Leutenegger ◽  
Jeannine Berger ◽  
Nicole Barat ◽  
John E. Madigan ◽  
...  
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Complete Blood Count ◽  
Clinical Manifestations ◽  
Clinical Severity ◽  
Human Granulocytic Anaplasmosis ◽  
High Passage ◽  
Granulocytic Anaplasmosis ◽  
Low Passage

ABSTRACT Anaplasma phagocytophilum causes human granulocytic anaplasmosis by inducing immunopathologic responses. Its immunodominant Msp2 protein is encoded by a family of >100 paralogs. Msp2 (msp2) expression modulates in the absence of immune pressure, and prolonged in vitro passage modulates in vivo virulence. Because programmed MSP2 expression occurs in Anaplasma marginale, we hypothesized a similar event in A. phagocytophilum in vivo, with specific Msp2 expression triggering immunopathologic injury or clinical manifestations of disease. We examined msp2 transcripts in 11 B6 mice and 6 horses inoculated with low- or high-passage A. phagocytophilum Webster strain. Blood was sequentially obtained through 3 weeks postinfection for msp2 reverse transcription-PCR. Horses were additionally assessed for clinical manifestations, seroconversion, complete blood count, blood chemistry, and cytokine gene transcription. In both species, there was no consistent emergence of msp2 transcripts, and all 22 msp2 variants were detected in both passage groups. Clinical severity was much higher for high-passage-infected than for low-passage-infected horses, preceded by higher levels of blood gamma interferon transcription on day 7. Antibody was first detected on day 7, and all horses seroconverted by day 22, with a trend toward lower antibody titers in low-passage-infected animals. Leukocyte and platelet counts were similar between experimental groups except on day 13, when low-passage-infected animals had more profound thrombocytopenia. These findings corroborate studies with mice, where msp2 diversity did not explain differences in hepatic histopathology, but differ from the paradigm of low-passage A. phagocytophilum causing more significant clinical illness. Alteration in transcription of msp2 has no bearing on clinical disease in horses, suggesting the existence of a separate proinflammatory component differentially expressed with changing in vitro passage.

scholarly journals Sialyl-Lewis x-Independent Infection of Human Myeloid Cells by Anaplasma phagocytophilum Strains HZ and HGE1

2007 ◽  
Vol 75 (12) ◽  
pp. 5720-5725 ◽  
Author(s):  
Madhubanti Sarkar ◽  
Dexter V. Reneer ◽  
Jason A. Carlyon
Keyword(s):  
Sialic Acid ◽  
Anaplasma Phagocytophilum ◽  
Myeloid Cells ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Bacterial Populations ◽  
Obligate Intracellular ◽  
Granulocytic Anaplasmosis ◽  
Sialyl Lewis ◽  
N Terminus

ABSTRACT Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligate intracellular bacterium that infects neutrophils and neutrophil precursors. Bacterial recognition of P-selectin glycoprotein ligand-1 (PSGL-1) and the α2,3-sialylated- and α1,3-fucosylated-moiety sialyl-Lewis x (sLex), which modifies the PSGL-1 N terminus, is important for adhesion to and invasion of myeloid cells. We have previously demonstrated that A. phagocytophilum organisms of the NCH-1 strain that utilize an sLex-modified PSGL-1-independent means of entry can be enriched for by cultivation in undersialylated HL-60 cells that are unable to construct sLex. Because it was unknown whether other A. phagocytophilum isolates share this ability, we extended our studies to the geographically diverse strains HZ and HGE1. HL-60 A2 is a clonal cell line that is defective for sialylation and α1,3-fucosyltransferase. HL-60 A2 cell surfaces, therefore, not only lack sLex but also are virtually devoid of any other sialic acid- and/or α1,3-fucose-modified glycan. By cultivating HZ and HGE1 in HL-60 A2 cells, we enriched for bacterial subpopulations (termed HZA2 and HGE1A2) that bind and/or infect myeloid cells in the absence of sialic acid and α1,3-fucose and in the presence of antibody that blocks the N terminus of PSGL-1. Thus, multiple A. phagocytophilum isolates share the ability to use sLex-modified PSGL-1-dependent and -independent routes of entry into myeloid cells. HZA2 and HGE1A2 represent enriched bacterial populations that will aid dissection of the complexities of the interactions between A. phagocytophilum and host myeloid cells.

scholarly journals Role of Bcl-2 Family Members in Caspase-Independent Apoptosis during Chlamydia Infection

2002 ◽  
Vol 70 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Jean-Luc Perfettini ◽  
John C. Reed ◽  
Nicole Israël ◽  
Jean-Claude Martinou ◽  
Alice Dautry-Varsat ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Chlamydia Psittaci ◽  
Host Cells ◽  
Chlamydia Infection ◽  
Caspase Inhibitor ◽  
Obligate Intracellular Bacterium ◽  
Obligate Intracellular ◽  
Infected Cells ◽  
Induced Apoptosis

ABSTRACT Infection with an obligate intracellular bacterium, the Chlamydia trachomatis lymphogranuloma venereum (LGV/L2) strain or the guinea pig inclusion conjunctivitis serovar of Chlamydia psittaci, leads to apoptosis of host cells. The apoptosis is not affected by a broad-spectrum caspase inhibitor, and caspase-3 is not activated in infected cells, suggesting that apoptosis mediated by these two strains of Chlamydia is independent of known caspases. Overexpression of the proapoptotic Bcl-2 family member, Bax, was previously shown to induce caspase-independent apoptosis, and we find that Bax is activated and translocates from the cytosol to the mitochondria in C. psittaci-infected cells. C. psittaci-induced apoptosis is inhibited in host cells overexpressing Bax inhibitor-1 and is inhibited through overexpression of Bcl-2, which blocks both caspase-dependent and -independent apoptosis. As Bax and mitochondria are ideally located to sense stress-related metabolic changes emanating from the interior of an infected cell, it is likely that Bax-dependent apoptosis may also be observed in cells infected with other intracellular pathogens.

scholarly journals FINDINGS OF THE ANAPLASMA PHAGOCYTOPILUM GENOME IN TICKS FROM VOJVODINA AREA, SERBIA

2013 ◽  
Vol 6 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Aleksandar Potkonjak ◽  
Sara Savić ◽  
Živoslav Grgić ◽  
Branislav Lako ◽  
Vuk Vračar ◽  
...  
Keyword(s):  
Public Health ◽  
Anaplasma Phagocytophilum ◽  
Human Population ◽  
Dermacentor Reticulatus ◽  
Wild Animals ◽  
Obligate Intracellular Bacterium ◽  
Gram Negative ◽  
Obligate Intracellular ◽  
Pcr Method ◽  
Autonomous Province

Ticks are vectors for many infectious diseases and represent a constant threat to human population and other animals, especially with respect to zoonoses. Th e cause of granulocyte anaplasmosis Anaplasma phagocytophilum is a gram-negative, obligate intracellular bacterium that infects people as well as various domestic and wild animals. Th e agent is spread worldwide, persisting in the natural environment through an enzootic circle between ticks and their hosting vertebrae. Th e aim of this paper is to demonstrate the distribution of ticks’ infection with Anaplasma phagocytophilum in the territory of the Autonomous Province of Vojvodina. Ticks were collected at ten locations in the Autonomous Province of Vojvodina, Serbia, which are a rural habitat for ticks. By applying the nested PCR method, the ticks were examined for the presence of specifi c DNA p44/msp2 Anaplasma phagocytphilum. Of the ten examined pools of ticks collected in the area of the Autonomous Province of Vojvodina, the presence of genome of the agent Anaplasma phagocytophilum was confi rmed in six pools applying the PCR method. In five pools of ticks of the species Ixodes ricinus, presence of agent Anaplasma phagocytophilum was confi rmed. Th ese ticks were found at the following locations: Poplar Research Institute (2 locations), Fruška gora (2 locations) Poloj-forest Bačka Palanka (1 location). In one pool of ticks of the species Dermacentor reticulatus from the location Poloj-forest Bačka Palanka, we confi rmed the presence of Anaplasma phagocytophilum genome. This infection can be a problem for public health, so further and more comprehensive acharological and epidemiological research is necessary in the Autonomous Province of Vojvodina.

scholarly journals Anchoring on COVID-19: A Case Report of Human Granulocytic Anaplasmosis Masquerading as COVID-19

2021 ◽  
Vol 5 (3) ◽  
pp. 328-331
Author(s):  
Mark Stice ◽  
Charles Bruen ◽  
Kristi Grall
Keyword(s):  
Case Report ◽  
Anaplasma Phagocytophilum ◽  
Inclusion Bodies ◽  
Severe Disease ◽  
Chain Reaction ◽  
Peripheral Smear ◽  
Severe Respiratory Distress ◽  
Human Granulocytic Anaplasmosis ◽  
Granulocytic Anaplasmosis ◽  
Polymerase Chain

Introduction: Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum and transmitted through the deer tick. Most cases are mild and can be managed as an outpatient, but rare cases can produce severe symptoms. Case Report: A 43-year-old male presented with severe respiratory distress mimicking coronavirus disease 2019 (COVID-19). Labs and imaging were consistent with COVID-19; however, polymerase chain reaction was negative twice. Peripheral smear revealed inclusion bodies consistent with HGA. Conclusion: Human granulocytic anaplasmosis is an uncommon diagnosis and rarely causes severe disease. Recognition of unique presentations can aid in quicker diagnosis, especially when mimicking presentations frequently seen during the COVID-19 pandemic.

scholarly journals Inhibition of Fusion of Chlamydia trachomatis Inclusions at 32°C Correlates with Restricted Export of IncA

2002 ◽  
Vol 70 (7) ◽  
pp. 3816-3823 ◽  
Author(s):  
K. A. Fields ◽  
E. Fischer ◽  
T. Hackstadt
Keyword(s):  
Chlamydia Trachomatis ◽  
Hela Cells ◽  
Immunofluorescence Microscopy ◽  
Parasitophorous Vacuole ◽  
Obligate Intracellular Bacterium ◽  
Inclusion Membrane ◽  
Obligate Intracellular ◽  
Transmission Electron ◽  
Infected Cells ◽  
Exocytic Pathway

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that develops within a parasitophorous vacuole termed an inclusion. The inclusion is nonfusogenic with lysosomes but intercepts lipids from a host cell exocytic pathway. Initiation of chlamydial development is concurrent with modification of the inclusion membrane by a set of C. trachomatis-encoded proteins collectively designated Incs. One of these Incs, IncA, is functionally associated with the homotypic fusion of inclusions. Inclusions also do not fuse when cultures are multiply infected with C. trachomatis and cultivated at 32°C. We obtained evidence linking these experimental observations by characterizing IncA localization in 32°C cultures. Analysis of inclusions by light and transmission electron microscopy confirmed that HeLa cells infected with multiple C. trachomatis elementary bodies and cultivated at 32°C for 24 h contained multiple, independent inclusions. Reverse transcriptase PCR and immunoblot analyses of C. trachomatis-infected HeLa cells demonstrated the presence of IncA at 24 h in 32°C cultures. When parallel cultures were probed with IncA-specific antibodies in indirect immunofluorescence assays, IncA was detectable in intracellular chlamydiae but not within the inclusion membrane. In addition, analysis of purified reticulate bodies from 37 and 32°C cultures showed that bacterium-associated pools of IncA are enriched in cultures grown at 32°C. Microscopic observation of infected cells revealed that some vacuoles had fused by 48 h postinfection, and this finding was correlated with the detection of IncA in inclusion membranes by immunofluorescence microscopy. The data are consistent with a requirement for IncA in fusions of C. trachomatis inclusions and suggest that the effect of incubation at 32°C is manifested by restricted export of IncA to the inclusion membrane.

scholarly journals PCR for detection of tick-borne Anaplasma phagocytophilum pathogens: a review

2011 ◽  
Vol 56 (No. 11) ◽  
pp. 529-536 ◽  
Author(s):  
A. Rymaszewska
Keyword(s):  
16S Rrna ◽  
Infectious Diseases ◽  
Natural Environment ◽  
Nested Pcr ◽  
Anaplasma Phagocytophilum ◽  
Emerging Infectious Diseases ◽  
Molecular Methods ◽  
Ecological Studies ◽  
Obligate Intracellular ◽  
Granulocytic Anaplasmosis

Tick-borne infections such as granulocytic anaplasmosis number among emerging infectious diseases. Anaplasma phagocytophilum is an obligate intracellular bacterial parasite infecting the granulocytes of vertebrates. This bacterium is the aetiologic agent of HGA (human granulocytic anaplasmosis). Molecular methods allow quick and accurate detection of pathogens in ticks, humans, or animals. Monitoring of the environment for A. phagocytophilum involves both classical and nested PCR, since these simple methods are most efficient. As markers, parts of the 16S rRNA, ankA, groESL, msp2, or msp4 genes are used for analyses. Molecular methods have enabled analysis of the genomes of pathogens, differentiation between strains and thus, in association with ecological studies, they facilitate an understanding of their biology, pathogenicity and mode of diffusion in the natural environment.  

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