Differential Clearance and Immune Responses to Tick Cell-Derived versus Macrophage Culture-Derived<i>Ehrlichia chaffeensis</i>in Mice

Ganta, Roman R.; Cheng, Chuanmin; Miller, Elizabeth C.; McGuire, Bridget L.; Peddireddi, Lalitha; Sirigireddy, Kamesh R.; Chapes, Stephen K.

doi:10.1128/iai.01127-06

Cited by 41 publications

(72 citation statements)

References 59 publications

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“…OD650nm, optical density at 650 nm. macrophages (9). Although proteomic analysis indicated the predominant expression of the P28-19 and P28-20 proteins of E. chaffeensis and their orthologs of E. canis in mammalian cells, reverse transcription-PCR (RT-PCR) analysis provided evidence for transcriptional activity of the majority of the genes within the p28 family (3,15,20).…”

Section: Discussionmentioning

confidence: 99%

Immunization with Ehrlichia P28 Outer Membrane Proteins Confers Protection in a Mouse Model of Ehrlichiosis

Crocquet‐Valdes

Thirumalapura

Ismail

et al. 2011

Clin Vaccine Immunol

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The obligately intracellular bacterium Ehrlichia chaffeensis that resides in mononuclear phagocytes is the etiologic agent of human monocytotropic ehrlichiosis (HME). HME is an emerging and often life-threatening, tick-transmitted infectious disease in the United States. Effective primary immune responses against Ehrlichia infection involve generation of Ehrlichia-specific gamma interferon (IFN-␥)-producing CD4 ؉ T cells and cytotoxic CD8؉ T cells, activation of macrophages by IFN-␥, and production of Ehrlichia-specific antibodies of the Th1 isotype. Currently, there are no vaccines available against HME. We evaluated the ability of 28-kDa outer membrane proteins (P28-OMP-1) of the closely related Ehrlichia muris to stimulate long-term protective memory T and B cell responses and confer protection in mice. The spleens of mice vaccinated with E. muris P28-9, P28-12, P28-19, or a mixture of these three P28 proteins (P28s) using a DNA prime-protein boost regimen and challenged with E. muris had significantly lower bacterial loads than the spleens of mockvaccinated mice. Mice immunized with P28-9, P28-12, P28-19, or the mixture induced Ehrlichia-specific CD4 ؉ Th1 cells. Interestingly, mice immunized with P28-14, orthologs of which in E. chaffeensis and E. canis are primarily expressed in tick cells, failed to lower the ehrlichial burden in the spleen. Immunization with the recombinant P28-19 protein alone also significantly decreased the bacterial load in the spleen and liver compared to those of the controls. Our study reports, for the first time, the protective roles of the Ehrlichia P28-9 and P28-12 proteins in addition to confirming previous reports of the protective ability of P28-19. Partial protection induced by immunization with P28-9, P28-12, and P28-19 against Ehrlichia was associated with the generation of Ehrlichia-specific cell-mediated and humoral immune responses.

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Section: Discussionmentioning

confidence: 99%

Immunization with Ehrlichia P28 Outer Membrane Proteins Confers Protection in a Mouse Model of Ehrlichiosis

Crocquet‐Valdes

Thirumalapura

Ismail

et al. 2011

Clin Vaccine Immunol

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“…Recently, E. chaffeensis Arkansas cultured in ISE6 tick cells was reported to persist 9 days longer in immunocompetent mice than the same bacteria cultured in DH82 cells persisted (15). Therefore, by finding more suitable culture conditions and E. chaffeensis strains more virulent than the Arkansas strain, we may be able to develop an immunocompetent mouse model of E. chaffeensis infection that allows investigation of the acquired immune response in the future.…”

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confidence: 99%

Virulence Potential of Ehrlichia chaffeensis Strains of Distinct Genome Sequences

Miura

Rikihisa

2007

Infect Immun

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Human monocytic ehrlichiosis, one of the most frequent life-threatening tick-borne zoonoses, is caused by Ehrlichia chaffeensis that lacks endotoxin and peptidoglycan. While sequence polymorphisms in several genes in E. chaffeensis strains have been reported, global genomic divergence and biological differences among strains are unknown. The objectives of the present study were to compare the genome sequences of strains of E. chaffeensis and to examine the virulence potentials of the strains with defined genome sequences. Genomic DNA was extracted from purified E. chaffeensis strains Wakulla and Liberty, and comparative genome hybridization was performed using a densely tiled microarray of 147,027 chromosome positions of the E. chaffeensis strain Arkansas genome. The results revealed that 4,663 and 5,325 positions in the chromosomes of strains Wakulla and Liberty, respectively, were different from those in the chromosome of strain Arkansas, including three common major polymorphic chromosomal regions. Of various functional categories, the differences were most concentrated in genes predicted to encode cell envelope proteins. Of all the open reading frames (ORFs), 21 omp-1 (p28 gene) paralogs, nine genes encoding hypothetical proteins, two genes encoding ankyrin repeat proteins, and hemE contained the most differences. Several highly polymorphic ORFs were confirmed by sequencing. When the E. chaffeensis strains were inoculated into severe combined immunodeficiency mice, the order of the severity of clinical signs and the bacterial burden detected in mice was Wakulla > Liberty > Arkansas. Severe diffuse inflammation and granulomatous inflammation were evident in the livers of mice infected with strains Wakulla and Arkansas, respectively, but not in the livers of mice infected with strain Liberty. These results revealed distinct virulence phenotypes of E. chaffeensis strains with defined genome sequences.

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“…Alterations that occur in the surface-exposed proteome upon the transition between host species are less well defined in Anaplasma and Ehrlichia spp., and investigations have been confined to a single protein family, pfam01617. However, comparison of expression of specific outer membrane proteins within this protein family has revealed host cell-dependent switching and shifts in levels of expression of these closely related proteins (6,27,31).…”

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confidence: 99%

Composition of the Surface Proteome ofAnaplasma marginaleand Its Role in Protective Immunity Induced by Outer Membrane Immunization

et al. 2008

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Surface proteins of tick-borne, intracellular bacterial pathogens mediate functions essential for invasion and colonization. Consequently, the surface proteome of these organisms is specifically relevant from two biological perspectives, induction of protective immunity in the mammalian host and understanding the transition from the mammalian host to the tick vector. In this study, the surface proteome of Anaplasma marginale, a tick-transmitted bacterial pathogen, was targeted by using surface-specific cross-linking to form intermolecular bonds between adjacent proteins. Liquid chromatography and tandem mass spectroscopy were then employed to characterize the specific protein composition of the resulting complexes. The surface complexes of A. marginale isolated from erythrocytes of the mammalian host were composed of multiple membrane proteins, most of which belong to a protein family, pfam01617, which is conserved among bacteria in the genus Anaplasma and the closely related genus Ehrlichia. In contrast, the surface proteome of A. marginale isolated from tick cells was much less complex and contained a novel protein, AM778, not identified within the surface proteome of organisms from the mammalian host. Immunization using the cross-linked surface complex induced protection against high-level bacteremia and anemia upon A. marginale challenge of cattle and effectively recapitulated the protection induced by immunization with whole outer membranes. These results indicate that a surface protein subset of the outer membrane is capable of inducing protective immunity and serves to direct vaccine development. Furthermore, the data support that remodeling of the surface proteome accompanies the transition between mammalian and arthropod hosts and identify novel targets for blocking transmission.

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Differential Clearance and Immune Responses to Tick Cell-Derived versus Macrophage Culture-DerivedEhrlichia chaffeensisin Mice

Cited by 41 publications

References 59 publications

Immunization with Ehrlichia P28 Outer Membrane Proteins Confers Protection in a Mouse Model of Ehrlichiosis

Immunization with Ehrlichia P28 Outer Membrane Proteins Confers Protection in a Mouse Model of Ehrlichiosis

Virulence Potential of Ehrlichia chaffeensis Strains of Distinct Genome Sequences

Composition of the Surface Proteome ofAnaplasma marginaleand Its Role in Protective Immunity Induced by Outer Membrane Immunization

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