Characterization of the non-specific humoral and cellular antiviral immunity stimulated by the chloroform-methanol residue (CMR) fraction of Coxiella burnetii

Zvilich, Menachem; Williams, Jim C.; Waag, David M.; Rill, Wayne R.; Malli, Robert; Bell, Paul; Kende, Meir

doi:10.1016/0166-3542(95)00022-e

Cited by 4 publications

(10 citation statements)

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“…The fold induction of transcript expression over untreated cells was calculated for IFN-␤ and IL-1␤, with normalization to ␤-actin transcripts. Consistent with findings described in the literature with extracts from phase I organisms (15,25), LPS from the virulent strain of C. burnetii increased expression of IFN-␤ transcripts by about 2-fold compared to human cells treated with control medium after stimulation for 12 h. Cells were also stimulated for 6 or 18 h, and this increased expression of IFN-␤ was not apparent at these intervals (Fig. 6).…”

Section: Induction Of Ifn-␤ Transcripts In Human Cells By Nmi Lps Stisupporting

confidence: 79%

“…The literature suggests C. burnetii has the capacity to trigger production of type I IFN, but the precise mechanism has not been determined (15,25). One way to induce the cytokine is LPS signaling through Toll-like receptor 4 (TLR4).…”

Section: Figmentioning

confidence: 99%

“…For example, injection of inactivated phase I C. burnetii cells protected mice from infection with a variety of type I IFN-sensitive viruses, but not a type I IFN-insensitive virus (15). Also, a fraction extracted from C. burnetii under investigation as a potential vaccine was proposed as a broad-spectrum antiviral prophylactic therapy because it strongly induced type I IFN and protected mice from viral infection (25). In this case, it was determined that both type I IFNs and IFN-␥ were induced by the fraction.…”

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confidence: 99%

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Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

et al. 2016

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Coxiella burnetii is an intracellular pathogen and the cause of Q fever. Gamma interferon (IFN-␥) is critical for host protection from infection, but a role for type I IFN in C. burnetii infection has not been determined. Type I IFN supports host protection from a related pathogen, Legionella pneumophila, and we hypothesized that it would be similarly protective in C. burnetii infection. In contrast to our prediction, IFN-␣ receptor-deficient (IFNAR ؊/؊ ) mice were protected from C. burnetii-induced infection. Therefore, the role of type I IFN in C. burnetii infection was distinct from that in L. pneumophila. Mice treated with a double-stranded-RNA mimetic were protected from C. burnetii-induced weight loss through an IFNAR-independent pathway. We next treated mice with recombinant IFN-␣ (rIFN-␣). When rIFN-␣ was injected by the intraperitoneal route during infection, disease-induced weight loss was exacerbated. Mice that received rIFN-␣ by this route had dampened interleukin 1␤ (IL-1␤) expression in bronchoalveolar lavage fluids. However, when rIFN-␣ was delivered to the lung, bacterial replication was decreased in all tissues. Thus, the presence of type I IFN in the lung protected from infection, but when delivered to the periphery, type I IFN enhanced disease, potentially by dampening inflammatory cytokines. To better characterize the capacity for type I IFN induction by C. burnetii, we assessed expression of IFN-␤ transcripts by human macrophages following stimulation with lipopolysaccharide (LPS) from C. burnetii. Understanding innate responses in C. burnetii infection will support the discovery of novel therapies that may be alternative or complementary to the current antibiotic treatment.

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Section: Induction Of Ifn-␤ Transcripts In Human Cells By Nmi Lps Stisupporting

confidence: 79%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

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Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

et al. 2016

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“…Type 1 IFN signaling has also been implicated in efficient clearance of group B Streptococcus , S. pneumoniae , and Escherichia coli (Textoris et al, 2012 ). Indeed, injection of C. burnetii components in mice induces a transient IFN-α/β production, and a steady synthesis of OAS for several days (Zvilich et al, 1995 ). This finding is potentially important for the defense against C. burnetii since type 1 IFN was either not detected or its pathway was defective in macrophages or dendritic cells stimulated by C. burnetii , respectively (Gorvel et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis

Faugaret

Amara

Alingrin

et al. 2014

Front. Cell. Infect. Microbiol.

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The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells (PBMCs) and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells of which more than 50% were commonly modulated genes in response to C. burnetii and BCG. They included M1-related genes and genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5, directly interfered with granuloma formation. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response. Our results showed that granuloma formation is associated with a core of transcriptional response based on inflammatory genes. The specific granulomatous response to C. burnetii is characterized by the activation of type 1 interferon pathway.

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“…CMR of C . burnetii can induce nonspecific immunoresponses, producing high levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in hosts [ 22 , 23 ], which inhibit viral, protozoan and bacterial infections via activation of bactericidal systems of macrophages and cytotoxicity of NK cells [ 24 ]. Furthermore, CMR of C .…”

Section: Introductionmentioning

confidence: 99%

Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice

et al. 2015

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The obligate intracellular bacteria, Rickettsia rickettsii and Coxiella burnetii, are the potential agents of bio-warfare/bio-terrorism. Here C3H/HeN mice were immunized with a recombinant protein fragment rOmp-4 derived from outer membrane protein B, a major protective antigen of R. rickettsii, combined with chloroform-methanol residue (CMR) extracted from phase I C. burnetii organisms, a safer Q fever vaccine. These immunized mice had significantly higher levels of IgG1 and IgG2a to rOmpB-4 and interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), two crucial cytokines in resisting intracellular bacterial infection, as well as significantly lower rickettsial loads and slighter pathological lesions in organs after challenge with R. rickettsii, compared with mice immunized with rOmpB-4 or CMR alone. Additionally, after challenge with C. burnetii, the coxiella loads in the organs of these mice were significantly lower than those of mice immunized with rOmpB-4 alone. Our results prove that CMR could markedly potentiate enhance the rOmpB-4-specific immunoprotection by promoting specific and non-specific immunoresponses and the immunization with the protective antigen of R. rickettsii combined with CMR of C. burnetii could confer effective protection against infection of R. rickettsii or C. burnetii.

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Characterization of the non-specific humoral and cellular antiviral immunity stimulated by the chloroform-methanol residue (CMR) fraction of Coxiella burnetii

Cited by 4 publications

References 24 publications

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis

Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice

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