General Information:

Id: 2,103
Diseases: Q fever
pathogen-host system
Coxiella burnetii/mammalia
review
Reference: Ghigo E et al.(2009) Intracellular life of Coxiella burnetii in macrophages Ann. N. Y. Acad. Sci. 1166: 55-66 [PMID: 19538264]

Interaction Information:

Comment Phase I, but not phase II, C. burnetii organisms (RSA493) survive in human monocytes and macrophages. Phase I organisms are poorly internalized by monocytes, whereas phase II variants are efficiently ingested.
Formal Description
Interaction-ID: 17118

organism

Coxiella burnetii, phase I

increases_activity of

process

pathogen survival

in human monocytes and macrophages
Comment Phase I, but not phase II, C. burnetii organisms (RSA493) survive in human monocytes and macrophages. Phase I organisms are poorly internalized by monocytes, whereas phase II variants are efficiently ingested.
Formal Description
Interaction-ID: 17123

organism

Coxiella burnetii, phase II

decreases_activity of

process

pathogen survival

in human monocytes and macrophages
Comment The uptake of phase II variants is mediated by alphav-beta3 integrin and CR3 (alphaM-beta2 integrin), whereas the internalization of phase I organisms involves the engagement of alphav-beta3 integrin, but not that of CR3.
Formal Description
Interaction-ID: 17124

organism

Coxiella burnetii, phase I

interacts (colocalizes) with

complex/PPI

Alphav-beta3 integrin complex

in human monocytes
Comment The uptake of phase II variants is mediated by alphav-beta3 integrin and CR3 (alphaM-beta2 integrin), whereas the internalization of phase I organisms involves the engagement of alphav-beta3 integrin, but not that of CR3.
Formal Description
Interaction-ID: 17125

organism

Coxiella burnetii, phase I

NOT interacts (colocalizes) with

complex/PPI

AlphaM-beta2 integrin complex

in human monocytes
Comment The uptake of phase II variants is mediated by alphav-beta3 integrin and CR3 (alphaM-beta2 integrin), whereas the internalization of phase I organisms involves the engagement of alphav-beta3 integrin, but not that of CR3.
Formal Description
Interaction-ID: 17128

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

complex/PPI

Alphav-beta3 integrin complex

in human monocytes
Comment The uptake of phase II variants is mediated by alphav-beta3 integrin and CR3 (alphaM-beta2 integrin), whereas the internalization of phase I organisms involves the engagement of alphav-beta3 integrin, but not that of CR3.
Formal Description
Interaction-ID: 17129

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

complex/PPI

AlphaM-beta2 integrin complex

in human monocytes
Comment The phagocytic efficiency of CR3 (alphaM-beta2 integrin) depends on its activation through alphav-beta3 integrin and CD47 (integrin-associated protein).
Formal Description
Interaction-ID: 17130

complex/PPI

Alphav-beta3 integrin complex

increases_activity of

complex/PPI

AlphaM-beta2 integrin complex

in human monocytes; in phase II organisms
Comment The phagocytic efficiency of CR3 (alphaM-beta2 integrin) depends on its activation through alphav-beta3 integrin and CD47 (integrin-associated protein).
Formal Description
Interaction-ID: 17134

gene/protein

CD47

increases_activity of

complex/PPI

AlphaM-beta2 integrin complex

in human monocytes; in phase II organisms
Comment The inhibition of the cross talk between alphav-beta3 integrin and CR3 (alphaM-beta2 integrin) induced by phase I organisms suggests that CR3 engagement is deleterious for C. burnetii.
Formal Description
Interaction-ID: 17136

complex/PPI

Alphav-beta3 integrin complex

NOT increases_activity of

complex/PPI

AlphaM-beta2 integrin complex

in human monocytes; in phase I organisms
Comment In monocytes, phase I C. burnetii organisms stimulate morphologic changes consisting of membrane protrusions and polarized projections. They increase their content in filamentous actin (F-actin) and induce an intense and transient rearrangement of F-actin.
Formal Description
Interaction-ID: 17137

organism

Coxiella burnetii, phase I

affects_activity of

in human monocytes
Comment Phase II organisms do not induce any change in cell morphology, actin polymerization, and F-actin organization.
Formal Description
Interaction-ID: 17139

organism

Coxiella burnetii, phase II

NOT affects_activity of

in human monocytes
Comment The efficiency of C. burnetii phagocytosis is dependent on the spatial distribution of CR3 (alphaM-beta2 integrin). CD11b (alphaM) and CD18 (beta 2) molecules, but not alphav-beta3 integrin, are excluded from the protrusions induced by C. burnetii in THP-1 monocytes. CR3 redistribution and increased bacterial uptake in RANTES-stimulated monocytes and Nef-expressing monocytes are associated with inhibited C. burnetii replication.
Formal Description
Interaction-ID: 17142

complex/PPI

AlphaM-beta2 integrin complex

decreases_activity of

process

Coxiella burnetii replication

in human monocytes
Comment Protein tyrosine kinases (PTK) down-modulate C. burnetii uptake by acting on actin cytoskeleton. Phase I bacteria induce early PTK activation and the tyrosine phosphorylation of several endogenous proteins, including Hck and Lyn, two Src-related kinases.
Formal Description
Interaction-ID: 17143

organism

Coxiella burnetii, phase I

increases_activity of

gene/protein

HCK

in human monocytes
Drugbank entries Show/Hide entries for HCK
Comment Protein tyrosine kinases (PTK) down-modulate C. burnetii uptake by acting on actin cytoskeleton. Phase I bacteria induce early PTK activation and the tyrosine phosphorylation of several endogenous proteins, including Hck and Lyn, two Src-related kinases.
Formal Description
Interaction-ID: 17145

organism

Coxiella burnetii, phase I

increases_activity of

gene/protein

LYN

in human monocytes
Drugbank entries Show/Hide entries for LYN
Comment PTK (protein tyrosine kinases) activation reflects C. burnetii virulence, since phase II bacteria do not stimulate PTK.
Formal Description
Interaction-ID: 17146

organism

Coxiella burnetii, phase II

NOT increases_activity of

gene/protein

Protein tyrosine kinase

in human monocytes
Comment During the course of C. burnetii infection, TLR4 controls the bacterial uptake by macrophages.
Formal Description
Interaction-ID: 17157

process

Coxiella burnetii infection

increases_activity of

gene/protein

TLR4

in human macrophages
Drugbank entries Show/Hide entries for TLR4
Comment Polymyxin B, which interferes with LPS binding, inhibits the uptake of phase I organisms without affecting the entry of phase II organisms.
Formal Description
Interaction-ID: 17158

drug/chemical compound

Polymyxin B

affects_activity of

organism

Coxiella burnetii, phase I

in human macrophages
Comment Besides its role in the uptake of phase I C. burnetii, TLR4 is also involved in C. burnetii-induced F-actin remodeling, highlighting again the close relationship between C. burnetii uptake and cytoskeletal organization.
Formal Description
Interaction-ID: 17159

gene/protein

TLR4

affects_activity of

in human macrophages
Drugbank entries Show/Hide entries for TLR4
Comment Besides its role in the uptake of phase I C. burnetii, TLR4 is also involved in C. burnetii-induced F-actin remodeling, highlighting again the close relationship between C. burnetii uptake and cytoskeletal organization.
Formal Description
Interaction-ID: 17160

process

Coxiella burnetii infection

affects_activity of

in human macrophages
Comment TLR4 controls the immune response against C. burnetii through granuloma formation and cytokine production. C. burnetii infection results in sustained formation of granulomas in wild-type mice, indicative of a protective immune response, but granuloma formation is only transient in TLR4-deficient mice.
Formal Description
Interaction-ID: 17161

gene/protein

TLR4

increases_activity of

in human macrophages; referred to early events of infection
Drugbank entries Show/Hide entries for TLR4
Comment In contrast to early events of C. burnetii infection, TLR4 is dispensable for bacterial survival in macrophages and bacterial clearance in vivo.
Formal Description
Interaction-ID: 17164

gene/protein

TLR4

NOT affects_activity of

process

pathogen survival

in human macrophages; referred to later events of infection
Drugbank entries Show/Hide entries for TLR4
Comment Similarly to TLR4, TLR2 is involved in the inflammatory and immune responses to C. burnetii, but is not necessary for bacterial clearance.
Formal Description
Interaction-ID: 17165

gene/protein

TLR2

NOT affects_activity of

process

pathogen survival

in human macrophages; referred to later events of infection
Drugbank entries Show/Hide entries for TLR2
Comment During the acute phase of Q fever, few, if any, isolated bacteria are found in granulomas. Granuloma formation is, at least in part, dependent on TLR4, since TLR4-deficient mice infected with C. burnetii display decreased numbers of granulomas.
Formal Description
Interaction-ID: 17170

disease

Q fever, acute

increases_activity of

in human monocytes and macrophages
Comment Chronic Q fever is characterized by an inefficient immune response. In contrast to acute Q fever, granulomas are lacking in chronic Q fever and infected tissues, including heart valves and liver, and aneurysms present large C. burnetii-containing vacuoles.
Formal Description
Interaction-ID: 17171

disease

Q fever, chronic

NOT increases_activity of

in human monocytes and macrophages
Comment It is likely that a atypical M2 macrophage activation program accounts for C. burnetii persistence in macrophages.
Formal Description
Interaction-ID: 17182

process

atypical M2 polarization

increases_activity of

process

pathogen survival

in human macrophages; described as atypical M2 macrophage activation program
Comment C. burnetii mainly induces the expression of M2 polarization-related genes, such as those encoding (TGF)-beta 1, IL-1 receptor antagonist (IL-1ra), CCL18, the mannose receptor, and arginase-1, even if organisms also induce the expression of genes encoding IL-6 and CXCL8, two cytokines associated with M1 program.
Formal Description
Interaction-ID: 17190

process

atypical M2 polarization

increases_quantity of

gene/protein

TGFB1

in macrophages
Drugbank entries Show/Hide entries for TGFB1
Comment C. burnetii mainly induces the expression of M2 polarization-related genes, such as those encoding (TGF)-beta 1, IL-1 receptor antagonist (IL-1ra), CCL18, the mannose receptor, and arginase-1, even if organisms also induce the expression of genes encoding IL-6 and CXCL8, two cytokines associated with M1 program.
Formal Description
Interaction-ID: 17193

process

atypical M2 polarization

increases_quantity of

gene/protein

IL1RN

in macrophages
Comment C. burnetii mainly induces the expression of M2 polarization-related genes, such as those encoding (TGF)-beta 1, IL-1 receptor antagonist (IL-1ra), CCL18, the mannose receptor, and arginase-1, even if organisms also induce the expression of genes encoding IL-6 and CXCL8, two cytokines associated with M1 program.
Formal Description
Interaction-ID: 17194

process

atypical M2 polarization

increases_quantity of

gene/protein

CCL18

in macrophages
Comment C. burnetii mainly induces the expression of M2 polarization-related genes, such as those encoding (TGF)-beta 1, IL-1 receptor antagonist (IL-1ra), CCL18, the mannose receptor, and arginase-1, even if organisms also induce the expression of genes encoding IL-6 and CXCL8, two cytokines associated with M1 program.
Formal Description
Interaction-ID: 17197

process

atypical M2 polarization

increases_quantity of

gene/protein

ARG1

in macrophages
Drugbank entries Show/Hide entries for ARG1
Comment C. burnetii-stimulated macrophages secrete high levels of (TGF)-beta 1 and CCL18, and express the mannose receptor and arginase-1, the latter being associated with the absence of nitric oxide release by macrophages.
Formal Description
Interaction-ID: 17204

process

atypical M2 polarization

increases_quantity of

gene/protein

MRC1

Comment C. burnetii inhibits the expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2.
Formal Description
Interaction-ID: 17208

process

M1 polarization

increases_quantity of

gene/protein

TNF

in macrophages
Drugbank entries Show/Hide entries for TNF
Comment C. burnetii inhibits the expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2.
Formal Description
Interaction-ID: 17209

process

M1 polarization

increases_quantity of

gene/protein

CD80

in macrophages
Drugbank entries Show/Hide entries for CD80
Comment C. burnetii inhibits the expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2.
Formal Description
Interaction-ID: 17210

process

M1 polarization

increases_quantity of

gene/protein

CCR7

in macrophages
Comment C. burnetii inhibits the expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2.
Formal Description
Interaction-ID: 17211

process

M1 polarization

increases_quantity of

gene/protein

TLR2

in macrophages
Drugbank entries Show/Hide entries for TLR2
Comment The M2 polarization, induced by the engulfment of apoptotic cells, express high levels of IL-10, IL-6, and CD14 in monocytes, the TNF levels are low.
Formal Description
Interaction-ID: 17212

process

M2 polarization

increases_quantity of

gene/protein

IL10

in monocytes
Comment The M2 polarization, induced by the engulfment of apoptotic cells, express high levels of IL-10, IL-6, and CD14 in monocytes, the TNF levels are low.
Formal Description
Interaction-ID: 17213

process

M2 polarization

increases_quantity of

gene/protein

IL6

in monocytes
Drugbank entries Show/Hide entries for IL6
Comment The M2 polarization, induced by the engulfment of apoptotic cells, express high levels of IL-10, IL-6, and CD14 in monocytes, the TNF levels are low.
Formal Description
Interaction-ID: 17214

process

M2 polarization

increases_quantity of

gene/protein

CD14

in monocytes
Comment Monocytes from patients with Q fever endocarditis and from patients with acute Q fever and valvulopathy overproduce IL-10. The risk of chronic evolution of the disease is associated with IL-10 overproduction.
Formal Description
Interaction-ID: 17215

disease

Q fever, chronic

increases_quantity of

gene/protein

IL10

in macrophages
Comment IL-10 alters leukocyte trafficking and, consequently, the formation of granulomas that is critical for protection against C. burnetii.
Formal Description
Interaction-ID: 17216

gene/protein

IL10

affects_activity of

in macrophages
Comment IL-10 alters leukocyte trafficking and, consequently, the formation of granulomas that is critical for protection against C. burnetii.
Formal Description
Interaction-ID: 17217

gene/protein

IL10

affects_activity of

in macrophages
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The first step of phagosome conversion is the intermingled fusion/fission with early endosomes, indicated by markers, such as early endosome antigen-1 (EEA1) and the small GTPase rab5.
Formal Description
Interaction-ID: 17280

gene/protein

EEA1

is localized in

cellular component

C. burnetii containing vacuole, CCV

associated with early endosome fusion
Drugbank entries Show/Hide entries for EEA1
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The first step of phagosome conversion is the intermingled fusion/fission with early endosomes, indicated by markers, such as early endosome antigen-1 (EEA1) and the small GTPase rab5.
Formal Description
Interaction-ID: 17281

gene/protein

RAB5

is localized in

cellular component

C. burnetii containing vacuole, CCV

associated with early endosome fusion
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The early phagosomes gradually transform into a compartment that present features of late endosomes. Markers of late endosomes, such as the small GTPase rab7 and lysosomal membrane-associated protein-1 (Lamp-1), progressively replace early endosomal markers.
Formal Description
Interaction-ID: 17282

gene/protein

RAB7

is localized in

cellular component

C. burnetii containing vacuole, CCV

associated with late endosome/lysosome fusion
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The early phagosomes gradually transform into a compartment that present features of late endosomes. Markers of late endosomes, such as the small GTPase rab7 and lysosomal membrane-associated protein-1 (Lamp-1), progressively replace early endosomal markers.
Formal Description
Interaction-ID: 17285

gene/protein

LAMP1

is localized in

cellular component

C. burnetii containing vacuole, CCV

associated with late endosome/lysosome fusion
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The pH of early phagosomes is around 6.0, the acquisition of vacuolar proton pump ATPase (V-H+-ATPase) allows the intraphagosomal pH to reach an acidic pH around 4.0.
Formal Description
Interaction-ID: 17287

complex/PPI

Vacuolar proton-transporting V-type ATPase complex

increases_activity of

Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. Late phagosomes interact with lysosomes that contain hydrolytic enzymes such as cathepsin D, thus leading to the formation of phagolysosomes.
Formal Description
Interaction-ID: 17290

increases_activity of

Comment Bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. Late phagosomes interact with lysosomes that contain hydrolytic enzymes such as cathepsin D, thus leading to the formation of phagolysosomes.
Formal Description
Interaction-ID: 17293

affects_quantity of

cellular component

C. burnetii containing vacuole, CCV

Comment Cathepsin D, a lysosomal protease, does not accumulate in phagosomes containing phase I C. burnetii. The lack of cathepsin D colocalization with phase I organisms is not due to a delayed acquisition, but rather to a defective fusion of phagosomes with lysosomes, as evidenced with a lysosomotropic probe.
Formal Description
Interaction-ID: 17300

organism

Coxiella burnetii, phase I

decreases_activity of

in human monocytes and macrophages
Comment Cathepsin D, a lysosomal protease, does not accumulate in phagosomes containing phase I C. burnetii. The lack of cathepsin D colocalization with phase I organisms is not due to a delayed acquisition, but rather to a defective fusion of phagosomes with lysosomes, as evidenced with a lysosomotropic probe.
Formal Description
Interaction-ID: 17301

organism

Coxiella burnetii, phase I

NOT interacts (colocalizes) with

gene/protein

CTSD

in human monocytes and macrophages
Drugbank entries Show/Hide entries for CTSD
Comment Cathepsin D, a lysosomal protease, does not accumulate in phagosomes containing phase I C. burnetii. The lack of cathepsin D colocalization with phase I organisms is not due to a delayed acquisition, but rather to a defective fusion of phagosomes with lysosomes, as evidenced with a lysosomotropic probe. The impaired acquisition of cathepsin D is related to bacterial virulence, since phase II organisms colocalize with cathepsin D.
Formal Description
Interaction-ID: 17302

organism

Coxiella burnetii, phase II

increases_activity of

in human monocytes and macrophages
Comment Cathepsin D, a lysosomal protease, does not accumulate in phagosomes containing phase I C. burnetii. The lack of cathepsin D colocalization with phase I organisms is not due to a delayed acquisition, but rather to a defective fusion of phagosomes with lysosomes, as evidenced with a lysosomotropic probe. The impaired acquisition of cathepsin D is related to bacterial virulence, since phase II organisms colocalize with cathepsin D.
Formal Description
Interaction-ID: 17303

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

gene/protein

CTSD

in human monocytes and macrophages
Drugbank entries Show/Hide entries for CTSD
Comment The survival of phase I C. burnetii is associated with impaired fusion of phagosomes with lysosomes in human monocytes.
Formal Description
Interaction-ID: 17304

decreases_activity of

process

pathogen survival

in human monocytes and macrophages
Comment TLR4 does not control the maturation of C. burnetii phagosomes.
Formal Description
Interaction-ID: 17305

gene/protein

TLR4

NOT affects_activity of

in human monocytes and macrophages
Drugbank entries Show/Hide entries for TLR4
Comment Adding IFN-gamma to C. burnetii-infected monocytes stimulates phagosome-lysosome fusion, but does not affect vacuolar pH.
Formal Description
Interaction-ID: 17312

gene/protein

IFNG

increases_activity of

in C. burnetii-infected monocytes
Drugbank entries Show/Hide entries for IFNG
Comment Monocytes from patients with chronic Q fever are unable to kill C. burnetii and exhibit a defective phagosome conversion. In contrast, monocytes from convalescent patients recovering from acute Q fever efficiently kill C. burnetii with a normal phagosome conversion.
Formal Description
Interaction-ID: 17314

disease

Q fever, chronic

increases_activity of

process

pathogen survival

in human monocytes
Comment Monocytes from patients with chronic Q fever are unable to kill C. burnetii and exhibit a defective phagosome conversion. In contrast, monocytes from convalescent patients recovering from acute Q fever efficiently kill C. burnetii with a normal phagosome conversion.
Formal Description
Interaction-ID: 17316

disease

Q fever, acute

decreases_activity of

process

pathogen survival

in human monocytes
Comment C. burnetii killing by monocytes and phagosome conversion are modulated by IL-10. The neutralization by specific antibodies of IL-10 in monocytes from patients with chronic Q fever increases C. burnetii killing and rescues phagosome conversion to the levels found in cured patients. In contrast, adding recombinant IL-10 to monocytes from patients with cured Q fever endocarditis prevents C. burnetii killing and induces phagosome conversion blockage.
Formal Description
Interaction-ID: 17318

gene/protein

IL10

increases_activity of

process

pathogen survival

in human monocytes
Comment C. burnetii killing by monocytes and phagosome conversion are modulated by IL-10. The neutralization by specific antibodies of IL-10 in monocytes from patients with chronic Q fever increases C. burnetii killing and rescues phagosome conversion to the levels found in cured patients. In contrast, adding recombinant IL-10 to monocytes from patients with cured Q fever endocarditis prevents C. burnetii killing and induces phagosome conversion blockage.
Formal Description
Interaction-ID: 17319

gene/protein

IL10

affects_activity of

in human monocytes
Comment Adding IFN-gamma to C. burnetii-infected monocytes stimulates phagosome-lysosome fusion, but does not affect vacuolar pH.
Formal Description
Interaction-ID: 32300

gene/protein

IFNG

NOT affects_activity of

in C. burnetii-infected monocytes
Drugbank entries Show/Hide entries for IFNG
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The pH of early phagosomes is around 6.0, the acquisition of vacuolar proton pump ATPase (V-H+-ATPase) allows the intraphagosomal pH to reach an acidic pH around 4.0.
Formal Description
Interaction-ID: 32935

increases_activity of

Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of genes encoding IL-6 and CXCL8, two cytokines associated with M1 program were also induced.
Formal Description
Interaction-ID: 34977

process

atypical M2 polarization

increases_quantity of

gene/protein

IL6

in macrophages
Drugbank entries Show/Hide entries for IL6
Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of genes encoding IL-6 and CXCL8, two cytokines associated with M1 program were also induced.
Formal Description
Interaction-ID: 34978

process

atypical M2 polarization

increases_quantity of

gene/protein

CXCL8

in macrophages
Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2 were inhibited.
Formal Description
Interaction-ID: 34979

process

atypical M2 polarization

NOT increases_quantity of

gene/protein

TNF

in macrophages
Drugbank entries Show/Hide entries for TNF
Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2 were inhibited.
Formal Description
Interaction-ID: 34980

process

atypical M2 polarization

NOT increases_quantity of

gene/protein

CD80

in macrophages
Drugbank entries Show/Hide entries for CD80
Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of M1 macrophage activation-associated genes such as those encoding TNF, CD80, CCR7, and TLR2 were inhibited.
Formal Description
Interaction-ID: 34981

process

atypical M2 polarization

NOT increases_quantity of

gene/protein

TLR2

in macrophages
Drugbank entries Show/Hide entries for TLR2
Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of arginase-1 has been associated with the absence of nitric oxide release by macrophages.
Formal Description
Interaction-ID: 34982

process

atypical M2 polarization

NOT increases_quantity of

drug/chemical compound

Reactive nitrogen species

in macrophages
Comment C. burnetii-stimulated macrophages induces the expression of M2 polarization-related genes. The expression of arginase-1 has been associated with the absence of nitric oxide release by macrophages.
Formal Description
Interaction-ID: 34983

gene/protein

ARG1

affects_quantity of

drug/chemical compound

Reactive nitrogen species

in macrophages
Drugbank entries Show/Hide entries for ARG1
Comment The uptake of apoptotic cells by myeloid cells is probably associated with chronic Q fever.
Formal Description
Interaction-ID: 35010

disease

Q fever, chronic

increases_activity of

Comment The binding of myeloid cells to apoptotic cells enhances C. burnetii replication and induces a M2 polarization. This M2 program shows slight differences between monocytes and macrophages.
Formal Description
Interaction-ID: 35011

increases_activity of

process

M2 polarization

in monocytes and macrophages
Comment The M2 polarization, induced by the engulfment of apoptotic cells, release high levels of TGF-beta-1 and mannose receptor in macrophages.
Formal Description
Interaction-ID: 35014

process

M2 polarization

increases_quantity of

gene/protein

TGFB1

in macrophages
Drugbank entries Show/Hide entries for TGFB1
Comment The M2 polarization, induced by the engulfment of apoptotic cells, release high levels of TGF-beta-1 and mannose receptor in macrophages.
Formal Description
Interaction-ID: 35015

process

M2 polarization

increases_quantity of

gene/protein

MRC1

in macrophages
Comment IFN-gamma induces the killing of phase I C. burnetii by naive monocytes.
Formal Description
Interaction-ID: 35019

gene/protein

IFNG

decreases_activity of

process

pathogen survival

by naive monocytes
Drugbank entries Show/Hide entries for IFNG
Comment Similarly to TLR4, TLR2 is involved in the inflammatory and immune responses to C. burnetii, but is not necessary for bacterial clearance.
Formal Description
Interaction-ID: 36042

process

Coxiella burnetii infection

affects_activity of

gene/protein

TLR2

in human macrophages
Drugbank entries Show/Hide entries for TLR2
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The first step of phagosome conversion is the intermingled fusion/fission with early endosomes, indicated by markers, such as early endosome antigen-1 (EEA1) and the small GTPase rab5.
Formal Description
Interaction-ID: 37439

gene/protein

EEA1

is localized in

cellular component

early endosome

Drugbank entries Show/Hide entries for EEA1
Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The first step of phagosome conversion is the intermingled fusion/fission with early endosomes, indicated by markers, such as early endosome antigen-1 (EEA1) and the small GTPase rab5.
Formal Description
Interaction-ID: 37440

gene/protein

RAB5

is localized in

cellular component

early endosome

Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The early phagosomes gradually transform into a compartment that present features of late endosomes. Markers of late endosomes, such as the small GTPase rab7 and lysosomal membrane-associated protein-1 (Lamp-1), progressively replace early endosomal markers.
Formal Description
Interaction-ID: 37441

gene/protein

RAB7

is localized in

cellular component

late endosome

Comment C. burnetii bacteria are localized within a compartment (phagosome) that undergoes a series of fusion/fission events with different populations of endocytic organelles such as endosomes. The early phagosomes gradually transform into a compartment that present features of late endosomes. Markers of late endosomes, such as the small GTPase rab7 and lysosomal membrane-associated protein-1 (Lamp-1), progressively replace early endosomal markers.
Formal Description
Interaction-ID: 37442

gene/protein

LAMP1

is localized in

cellular component

late endosome

Comment PTK (protein tyrosine kinases) and Src kinase (Hck, Lyn) inhibitors block the formation of cell protrusions and F-actin remodeling induced by phase I C. burnetii.
Formal Description
Interaction-ID: 37509

gene/protein

HCK

affects_activity of

in monocytes; induced by phase I C. burnetii
Drugbank entries Show/Hide entries for HCK
Comment PTK (protein tyrosine kinases) and Src kinase (Hck, Lyn) inhibitors block the formation of cell protrusions and F-actin remodeling induced by phase I C. burnetii.
Formal Description
Interaction-ID: 37513

gene/protein

LYN

affects_activity of

in monocytes; induced by phase I C. burnetii
Drugbank entries Show/Hide entries for LYN
Comment Protein tyrosine kinases (PTK) down-modulate C. burnetii uptake by acting on actin cytoskeleton. Phase I bacteria induce early PTK activation and the tyrosine phosphorylation of several endogenous proteins, including Hck and Lyn, two Src-related kinases.
Formal Description
Interaction-ID: 37514

organism

Coxiella burnetii, phase I

increases_activity of

gene/protein

Protein tyrosine kinase

in monocytes
Comment PTK (protein tyrosine kinases) and Src kinase (Hck, Lyn) inhibitors block the formation of cell protrusions and F-actin remodeling induced by phase I C. burnetii.
Formal Description
Interaction-ID: 37515

gene/protein

Protein tyrosine kinase

affects_activity of

in monocytes; induced by phase I C. burnetii
Comment Polymyxin B, which interferes with LPS binding, inhibits the uptake of phase I organisms without affecting the entry of phase II organisms.
Formal Description
Interaction-ID: 37519

drug/chemical compound

Polymyxin B

NOT affects_activity of

organism

Coxiella burnetii, phase II

in human macrophages
Comment Adding IFN-gamma to C. burnetii-infected monocytes stimulates phagosome-lysosome fusion, but does not affect vacuolar pH. The treatment of monocytes by IFN-gamma prior C. burnetii infection induces the alkalinization of C. burnetii vacuoles independently of the V-H+-ATPase exclusion.
Formal Description
Interaction-ID: 37802

gene/protein

IFNG

affects_activity of

in C. burnetii-infected monocytes; treated with IFN-gamma prior to infection
Drugbank entries Show/Hide entries for IFNG
Comment In monocytes, phase I C. burnetii organisms stimulate morphologic changes consisting of membrane protrusions and polarized projections. They increase their content in filamentous actin (F-actin) and induce an intense and transient rearrangement of F-actin.
Formal Description
Interaction-ID: 37813

organism

Coxiella burnetii, phase I

increases_activity of

in human monocytes